CAR T-Cell Therapy Offers Potential Solution for Relapse in MCL, But With Toxicity Risk – Targeted Oncology

Mantle cell lymphoma (MCL) accounts for 5% to 10% of all non-Hodgkin lymphomas (NHLs) and is commonly diagnosed when a patients disease is in an advanced stage with extranodal involvement, commonly including gastrointestinal mucosa and central nervous system involvement with blastoid variant. Disease relapse among patients with MCL is known to occur after prolonged remission, which leaves an unanswered question among oncologists in the field of how to approach treatment of relapsed MCL.1

In a presentation during the 2020 Debates and Didactics in Hematology and Oncology conference, Amelia A. Langston, MD, professor and executive vice chair, Department of Hematology and Medical Oncology; director, Bone Marrow and Stem Cell Transplant Program; and medical director, Winship Cancer Network, at Winship Cancer Institute of Emory University, explained the issues with treating patients with relapsed MCL and how the integration of chimeric antigen receptor (CAR) T-cell therapy can be a solution to the problem.

Langston noted that MCL has multiple morphologic variants, including classical disease, aggressive or blastoid disease, and indolent disease. Although it is common for oncologists to treat patients with indolent tumors right after diagnosis, Langston highlighted that a small proportion of those patients do not require immediate treatment.

One method for understanding when to start treatment and to predict how patients with MCL will respond to treatment, is utilizing the MIPIc (Mantle Cell Lymphoma International Prognostic Index) prognostic score. Another method, Langston explained, is through gene expression profiles, karyotype, and mutation analysis, which can identify p53 mutations, NOTCH-1 mutations, complex karyotype, and overall poor prognosis.

The primary treatment for MCL is aggressive induction followed by autologous stem cell transplantation (ASCT), which has been shown to prolong survival in patients with MCL who are fit for aggressive treatment.

Research by Martin Dreyling, MD, PhD, et al presented in 2005 demonstrated the feasibility of early consolidation with myeloablative radiochemotherapy followed by ASCT. In the study, 62 patients underwent ASCT, and 122 patients received interferon (IFN) alpha. With ASCT, the median progression-free survival (PFS) was 39 months with ASCT versus 17 months with IFN-alpha (P = .0108). The 3-year overall survival (OS) rate with ASCT was 83% versus 77% with IFN-alpha (P = .18).2

Data presented at the American Society of Hematology Annual Meeting in 2009 showed a median OS of 90 months with ASCT compared with 54 months with IFN (P = .034).3

Once patients with MCL relapse, the treatment landscape includes FDA-approved targeted therapies, chemotherapy/immunotherapy combinations, and allogeneic hematopoietic stem cell transplant. The targeted therapies include Brutons tyrosine kinase (BTK) inhibitors, proteasome inhibitors, immunomodulatory drugs, mTOR inhibitors, venetoclax (Venclexta), as well as combination regimens.

The BTK inhibitor ibrutinib (Imbruvica) at a 560-mg daily dose level has led to an objective response rate (ORR) of 66% with a complete response (CR) rate of 20%, according to a pooled analysis of 3 open-label clinical trials, which were the PCYC1104 (NCT01236391), SPARK (NCT01599949), and RAY (NCT01646021) studies. The analysis included 370 patients with MCL who had a median of 2 prior lines of therapy before receiving ibrutinib. This analysis also showed that more than 1 line of prior therapy, p53 mutations, and blastoid histology were all predictors of poor response to ibrutinib.4,5

Acalabrutinib (Calquence), another BTK inhibitor, at a dose of 100 mg twice daily demonstrated efficacy in a single-arm multicenter, phase 2 clinical trial (ACE-LY-004, NCT02213926). The ACE-LY-004 study included 124 patients with a median 2 prior lines of therapy. The ORR achieved with acalabrutinib was 81% (95% CI, 73%-87%) per investigator assessment. The CR rate was 40% (95% CI, 31%-49%).6

In terms of survival, the 12-month PFS rate observed with acalabrutinib was 67% (range, 58%-75%) and the 12-months OS rate was 87% (range, 79%-92%).

The adverse events observed in ACE-LY-004 were considered tolerable and only led to treatment discontinuation in 6% of the study population.

Investigators led by Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, concluded from this study that acalabrutinib holds an important place in the treatment landscape of MCL and induces a high rate of durable responses with tolerable safety.

For combination therapies in the MCL paradigm, ibrutinib plus venetoclax was investigated in a single-arm, multicenter, phase 2 study (AIM, NCT02471391), which enrolled 24 patients with MCL, 23 of whom had relapsed or refractory disease and 1 patient with a p53 mutation who was ineligible for chemotherapy. The median number of prior lines of therapy for this study population was 2, and 46% of patients had a p53 mutation and/or deletion. Ibrutinib was administered at 560 mg per day for 4 weeks and then venetoclax was added with a gradual dose escalation up to 400 mg per day.7

The combination of ibrutinib and venetoclax achieved a CR rate of 42% at 16 weeks, which surpassed the historical result of ibrutinib monotherapy (9%; P < .001). In addition, the CR rate among patients who were negative for minimal residual disease was 38%, and for patients with a p53 mutation, the CR rate was 50%. Ibrutinib plus venetoclax also achieved a PFS rate of 78% at 15 months.

The safety analysis did reveal 2 cases of tumor lysis syndrome in patients, however, but overall, the combination was well tolerated.

CAR T-cell therapy has already been integrated into the treatment landscape of many hematologic malignancies and is now being considered as a treatment for different solid tumors. CAR T-cell therapy is also a valid option for treatment of R/R MCL, and one agent, KTE-X19 has been granted Priority Review by the FDA for this indication based on results from the phase 2 ZUMA-2 trial.1

The multicenter study enrolled 74 patients and 68 of them received the CAR T-cell product. Among the MCL subjects, the subgroups included patients who relapsed after ASCT, relapsed after their most recent previous therapy, were refractory to BTK inhibition, relapsed during or after BTK inhibition, and could not receive BTK inhibition.8

In terms of efficacy, 85% of patients achieved an objective response, which included CRs in 59% of patients. In the various subgroups of patients with MCL included in the study, high rates of objective response were also observed. There were also 2 patients with stable disease and 2 with progressive disease.

Neither the median PFS nor OS were reached at the time of data cutoff, but the PFS rate at 1 year was estimated to be 61% in the study, and the OS rate was estimated to be 83% at 1 year.

The CAR T-cell agent led to grade 3 or higher AEs, the majority of which were cytopenias (94%); additionally, 32% were infections, 31% were neurologic events, 15% of patients had cytokine release syndrome, and 32% had hypogammaglobulinemia. The treatment-related mortality rate in this study was 3%, which was due to infections.

These data led to the conclusion that although KTE-X19 can induce durable remissions in patients with MCL, it causes serious toxicities that are common for CAR T-cell therapy. Thus, Langston noted in her presentation that CAR T-cell therapy for relapsed disease should only be considered for select patients.

Overall, BTK inhibition will likely remain a standard of care for R/R MCL, Langston stated, but CAR T-cell therapy should be carefully integrated into the landscape, once the first agent is granted FDA approval and depending on the indications of that approval. Finally, healthier patients with R/R MCL can continue to be considered for ASCT, which, she noted, has curative ability for heavily pretreated patients.1

References:

1. Langston AA. Integrating CAR t cell therapy into the management of relapsed mantle cell lymphoma. Presented at: 2020 Debates and Didactics in Hematology and Oncology; July 16-18, 2020; Sea Island, GA.

2. Dreyling M, Lenz G, Hoster E, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005;105(7):2677-2684. doi:10.1182/blood-2004-10-3883

3. Hoster E, Metzner B, Forstpointner R, et al. Autologous Stem Cell Transplantation and Addition of Rituximab Independently Prolong Response Duration in Advanced Stage Mantle Cell Lymphoma. Blood. 2009;114(22):880. doi:10.1182/blood.V114.22.880.880

4. Rule S, Dreyling M, Goy A, et al. Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies. Br J Haematol. 2019;179(3):430-438. doi:10.1111/bjh.14870

5. Rule S, Dreyling M, Goy A, et al. Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis. Haematologica. 2019;104(5):e211-e214. doi:10.3324/haematol.2018.205229

6. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2017;391(10121):659-667. doi:10.1016/S0140-6736(17)33108-2

7. Tam CS, Andeson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378(13):1211-1223. doi:10.1056/NEJMoa1715519

8. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR t-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331-1342. doi:10.1056/NEJMoa1914347

The rest is here:
CAR T-Cell Therapy Offers Potential Solution for Relapse in MCL, But With Toxicity Risk - Targeted Oncology

Fine-tuning adoptive cell therapy for advanced cancers – Newswise

FINDINGS

Newswise Adoptive cell transfer immunotherapy is one of the most promising new treatments for people with hard-to-treat cancers. However, the process is complex and needs fine-tuning in order to develop more treatment strategies that will work for more people.

In a new study looking at adoptive cell transfer products bearing a transgenic T-cell receptor (TCR), researchers at the UCLA Jonsson Comprehensive Cancer Center have identified a discordant phenomenon in which a subset of patients displayed profoundly decreased expression of the transgenic TCR over time, despite the transgenic TCR being present at the DNA level. This gave rise to the observation that structural changes to the DNA via DNA methylation make it inaccessible for transcription and translation, which is an influential step in the flow of genetic information from DNA to RNA. This can be one clue into why some patients stop responding to this type of immunotherapy.

The issue is this phenomenon happens over time, said lead author Theodore Scott Nowicki, MD, PhD, clinical instructor of pediatrics and hematology/oncology at the David Geffen School of Medicine at UCLA. Were hoping this can help inform the design of future generations of these types of therapies and pinpoint different vectors that might be more or less vulnerable to this phenomenon.

JOURNAL

The study waspublished onlinein Cancer Discovery, a journal of the American Association for Cancer Research.

BACKGROUND

Adoptive cell transfer immunotherapy works by taking a patients own T cells, which are one of the components of the immune system, and genetically modifying them in the laboratory to target tumor-specific antigens on the surface of the tumor. The new army of tumor-specific T cells are then reinfused back into the patient to help attack the cancer.

A key component of adoptive cell transfer therapy requires genetically modifying T cells to target cancer cells. This is often done with viral transduction agents with either lentivirus- or retrovirus-based products to express either a cancer antigen-specific TCR or chimeric antigen receptor (CAR).

In order to develop more efficient cell therapies, Nowicki and colleagues are studying the genetic mutations of T cells to understand the structural changes to DNA over time. This could reveal why adoptive cell transfer therapy is more likely to work in some patients versus others and help inform the future design of next-generations of the therapy.

METHOD

The team analyzed 16 clinical transgenic adoptive cell therapy samples collected before and during treatment from patients with melanoma and sarcoma. This allowed the team to look at the expression of the transgenic TCR at the DNA and protein level. It gave them insight into what proportion of the cells displayed impaired expression of the transgenic TCR. They were then able to assess the degree of DNA methylation present in the retroviral vectors promoter region over time, and correlate this degree of DNA methylation with repression of the transgenic TCR.

IMPACT

The study can help researchers in the design of future generations of cellular immunotherapies to help treat people with advanced cancers.

AUTHORS

The studys lead and senior author is Dr. Nowicki. The study was conducted under the mentorship of Dr. Antoni Ribas, professor of medicine and director of the tumor immunology program at the UCLA Jonsson Comprehensive Cancer Center. Both Dr. Nowicki and Dr. Ribas are members of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research. Other authors include Colin Farrell, Marco Morselli, Liudmilla Rubbi, Katie Campbell, Mignonette Macabali, Beata Berent-Maoz, Begona Comin-Anduix and Matteo Pellegrini, all of UCLA.

FUNDING

The research was funded in part by grants from the National Institutes of Health, the Tower Cancer Research Foundation, the Hyundai Hope on Wheels foundation, the Parker Institute for Cancer Immunotherapy and the Ressler Family Fund.

***

The UCLA Jonsson Comprehensive Cancer Center has more than 500 researchers and clinicians engaged in cancer research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the UCLA Jonsson Comprehensive Cancer Center is dedicated to promoting research and translating basic science into leading-edge clinical studies.

Read more from the original source:
Fine-tuning adoptive cell therapy for advanced cancers - Newswise

Global Cart Cell Therapy Market To Grow At A CAGR of 29.4% With The Emergence Of Immunotherapies In Medical Treatment – GlobeNewswire

July 22, 2020 08:41 ET | Source: Quince Market Insights

Pune, India, July 22, 2020 (GLOBE NEWSWIRE) -- The global cart cell therapy market size was valued at USD 355.1 million in 2018 and is anticipated to grow at a CAGR of 29.4% during the forecast period. For years, the foundations of cancer treatment were chemotherapy, surgery, and radiation therapy. With the development of targeted therapies like trastuzumab (Herceptin) and imatinib (Gleevec), drugs that target cancer cells have cemented themselves as standard treatments for many types of cancers.

Request For a Sample Copy Of This Research Report @ https://www.quincemarketinsights.com/request-sample-61563

But in recent years, immunotherapy has emerged as the "fifth pillar" of cancer treatment. The use of CAR T-cell clinical trials has captured the attention of researchers and the public alike because of the remarkable responses they have produced in both children and adults. Studies of CAR T-cell therapy in other blood cancers and treatment of solid tumors is also underway, researchers are exploring the application of CAR T-cell therapy.

The COVID-19 Impact on the Global Cart Cell Therapy Market

CAR-T and TCR-T therapies have revolutionized blood cancer treatment. Scientists at Duke-NUS Medical School are studying the potential of turning this approach for the treatment of COVID-19 patients.

Researchers suggest these immunotherapies might also be useful in treating SARS-CoV-2, the virus causing the current pandemic. Several organizations are also working on cell therapies for COVID-19. AlloVir and Baylor College of Medicine have partnered to develop an off-the-shelf therapy to target and treat the novel coronavirus.

The battle against COVID-19 is taking place across thousands of fronts in the U.S., from underfunded rural regional hospitals to the steel and glass high-rises of well-endowed university centers. What becomes clear when speaking with clinicians across the nation is that the effect of the pandemic on the delivery of CAR T-cell therapy depends on the type of center that provides it, as well as its location.

There were some initial delays providing CAR T-cell treatments at Mayo Clinic in Rochester, Minnesota, but they were short-lived and imposed in the name of patient safety as the institution looked to acquire an accurate diagnostic test to determine which patients had COVID-19.

CD19 to Lead the Target Antigen Segment of the Cart Cell Therapy Market

As per the current market scenario in 2018, the CD19 segment has covered the largest cart cell therapy market share and is projected to register a higher CAGR during the forecast period.

Besides, the growing need for integrated healthcare systems is responsible for the high demand for CD19 in the global cart cell therapy market.

Enquiry Before Buying This Report @ https://www.quincemarketinsights.com/enquiry-before-buying/enquiry-before-buying-61563

Cart Cell Therapy to Benefit Treatment of Blood Cancer Propelling the Growth of the Market

The application for the generation of revenues in the global cart cell therapy market is acute lymphoblastic leukemia, diffuse large b-cell lymphoma, and others. The acute lymphoblastic leukemia segment is predicted to account for the largest share. Cart Cell Therapy provides alternative therapeutic options for patients who failed to respond to conventional treatment or relapse for acute lymphoblastic leukemia which is a type of blood cancer.

Increasing Research Studies and Clinical Trials to Fuel the Growth of the Healthcare Segment

In 2018, healthcare accounted for the largest share of the end-user segment. As cart cell therapy improves clinical outcomes by helping to improve disease management. This will result in a shorter duration of hospitalization and overall physician observation hours.

North America Held a Major Market Share of the Global Cart Cell Therapy Market

North America holds a dominant position in the global cart cell therapy market. The region's dominance is attributable to favorable government policies for the prevention of disease and HCIT adoption, increasing funding for population health management, raising prevalence of chronic diseases, and the presence of well-developed healthcare infrastructure. For Instance, in 2010, the U.S. government implemented the Patient Protection and Affordable Care Act which encourages a high quality of care and reduces costs. The act has encouraged the creation of Accountable Care Organizations (ACOs), including the Medicare Shared Savings Program (MSSP).

Buy Now Complete Report @ https://www.quincemarketinsights.com/insight/buy-now/cart-cell-therapy-market/single_user_license

Companies Collaborate & Promote R&D along with Product Development

Cart Cell Therapy Market vendors are making substantial efforts in adopting advanced technologies essentially by allying and partnering that will help to facilitate the demand for Cart Cell Therapy.

Key participants include operating in the market include Bellicum Pharmaceuticals, Kite Pharma, Novartis AG, Mustang Bio, CARsgen Therapeutics, Sorrento Therapeutics, Autolus Therapeutics, Cellectis, Pfizer Inc., Legend Biotech, and others.

Search Important insights on Cart Cell Therapy Industry, By Region (Western Europe, North America, Eastern Europe, Middle East, Asia Pacific, and the Rest of the World), by End User (Pharmaceuticals, Hospital, Clinic and Others), By Target Antigen (CD22, CD19, and Others), and Application (Diffuse Large B-Cell Lymphoma, Acute Lymphoblastic Leukemia, and Others) Market Forecast & Assessment (2017-2028).

Browse Related Reports

Regenerative Medicine Market, By Type (Cell-Based Immunotherapy & Cell Therapy Products, Tissue-Engineered Products, Gene Therapy Products), Application (Wound Care, Musculoskeletal Disorders, Oncology, Ocular Disorders, Diabetes, Other Applications), and By Region (North America, Western Europe, Eastern Europe, Asia Pacific, Middle East, and the Rest of the World) Market Size & Forecasting (2017-2028)

https://www.quincemarketinsights.com/industry-analysis/regenerative-medicine-market/44444

Nerve Repair and Regeneration Market, By Products (Biomaterials, Nerve Conduits, Nerve Protectors, Nerve Wraps, Neurostimulation Devices) By Application (Neurorrhaphy, Nerve Grafting, Stem Cell Therapy, Neurostimulation Surgery),By Region (North America, Western Europe, Eastern Europe, Asia Pacific, Middle East, Rest of the World) Global Market Size & Forecasting(2016-2028)

https://www.quincemarketinsights.com/industry-analysis/nerve-repair-and-regeneration-market/59253

Cell Therapy And Tissue Engineering Market, By Type (Cell Therapy, Tissue Engineering, Others), By Application (Cell Defects, Genetic Diseases, Tissue Malignancy, Neurodegenerative Disease, Others), By Region (North America, Eastern Europe, Western Europe, Asia Pacific, Middle East, Rest Of The World) Market Size & Forecasting (2016-2028)

https://www.quincemarketinsights.com/industry-analysis/cell-therapy-and-tissue-engineering-market/60291

Autologous Cell Therapy Market, By Source (Bone Marrow, Epidermis), By Application (Neurology, Orthopedics, Cancer, Wound Healing, CVD, Autoimmune), By End User (Hospitals, Ambulatory Centers, Research Centers), By Region (North America, Eastern Europe, Western Europe, Asia Pacific, Middle East, Rest of the World) Market Size & Forecasting(2016-2028)

https://www.quincemarketinsights.com/industry-analysis/autologous-cell-therapy-market/60721

Culture Media Market, By Type (Lysogeny Broth, Chemically Defined Media, Classical Media, Serum-free Media, Specialty Media, Stem Cell Media, Custom Media Formulation, Others), By Application (Cancer Research, Biopharmaceuticals, Regenerative Medicine & Tissue Engineering, Stem Cell Technologies, Drug Discovery, Others), By Research Type (Cytogenetics, Cell Therapy, Others), By End User (Biotechnology & Pharmaceutical Industry, Academic Institute, Research Laboratory, Others), By Region (North America, Western Europe, Eastern Europe, Asia Pacific, Middle East, Rest of the World) Market Size & Forecasting (2016-2028)

https://www.quincemarketinsights.com/industry-analysis/culture-media-market/60933

About US

Quince Market Insights is a global market research and consulting company publishing syndicate studies as well as consulting assignments pertaining to markets that promise high growth opportunities in strategic future. We are dedicated team of analysts with strong base in technical expertise as well as thorough understanding of the market dynamics. Some of key areas expertise includes chemicals, advanced materials, construction, mining, food & agriculture, automotive, machines & equipment, and others. We analyze emerging trends in relatively nascent markets that promise high growth opportunities in future. We focus towards precision research practices that provide accurate market estimations and forecasts. This helps our clients to make proper estimations with regards to demand analysis, regional growth, major competitors, and dynamics of the market.

Read the rest here:
Global Cart Cell Therapy Market To Grow At A CAGR of 29.4% With The Emergence Of Immunotherapies In Medical Treatment - GlobeNewswire

In Remission for 10 Years: Long-term Data on CAR-T Therapy – Medscape

When a patient with cancer hears there isn't much left that doctors can do, it always stays fresh in the mind.

Doug Olson was first diagnosed with chronic lymphocytic leukemia (CLL) over 20 years ago, in 1996. For several years, his doctors used the watch-and-wait approach. But then his cancer progressed and needed treatment. By 2010, it had mutated so much that it no longer responded to standard therapy.

He was rapidly running out of options. Back then, the only treatment left was a bone marrow transplant. Without one, his doctors said, he would have 1 or 2 years left to live.

"I was really trying to avoid a bone marrow transplant. You're playing your last card if that doesn't work. It's a pretty rough procedure," Olson told Medscape Medical News.

Looking back, Olson counts himself as lucky for being in the right place, at the right time, with the right doctor. His oncologist was David Porter, MD, the principal investigator on a trial at the University of Pennsylvania that was investigating a brand new approach to treating cancer: chimeric antigen receptor (CAR) T-cell therapy.

CAR T-cell therapy uses a patient's own T cells engineered to express a receptor that targets proteins on cancer cells. CAR T cells are considered "living drugs" because they expand inside the body and stick around for years maybe for a lifetime to fight the cancer if it tries to come back.

"I was certainly intrigued by the approach. It had worked in mice, and it was the sort of thing that looked like it would work," Olson recalled.

Science is not a foreign language to Olson. He holds a PhD in medicinal chemistry, spent most of his career in the in vitro diagnostics industry, and currently acts as chief executive officer of Buhlmann Diagnostics Corp.

So he read the clinical protocol for the first in-human trial of CAR T cells and agreed to become patient number two.

Olson's T cells were harvested, engineered to attack the CD19 antigen found on malignant and normal B lymphocytes, and then were expanded into millions in the lab. After undergoing preconditioning with chemotherapy to minimize rejection and boost the CAR T cells' expansion inside the body, he received several infusions of the new therapy over the course of 3 days.

Nothing really happened for 2 weeks. Then he developed severe flu-like symptoms so bad that he was hospitalized.

Ironically, getting sick was a sign that the CAR T cells were working. Olson was experiencing one of the main short-term effects of CAR T-cell therapy: cytokine release syndrome. Symptoms include extremely high fevers and dangerous drops in blood pressure that can potentially cause end-organ damage.

In the early trials of these products, some patients experienced such a severe reaction that they needed intensive care, and some died. With increasing clinical experience, doctors have learned to control the reaction with the use of steroids and interleukein-6 inhibitors such as tocilizumab (Actemra).

Fortunately for Olson, the reaction passed, and he was eventually discharged.

Then the "aha moment" happened. Four weeks after receiving the CAR T cells, Olson found out that he was cancer free.

"It still gives me shivers," he said. "Dr Porter said, 'Your bone marrow's completely free. We just can't find a cancer cell anywhere.' "

The remission has lasted, and it is now 10 years later.

Long-term data have been accumulating for these novel therapies since Olson's treatment in 2010. This is particularly important for CAR T-cell therapy, because of its longevity. Because these are living cells and are expected to persist in the body for years, there is great interest in longer-term data, especially the risks for toxicity.

The FDA requires clinical follow-up for at least 15 years for patients treated with CAR T-cell therapy or any other genetically modified cells.

So far, most of the experience with CAR T cells comes from anti-CD19-directed therapy, which has shown "remarkable" remission rates in the 50% to 85% range, said Nirali Shah, MD, head of the hematologic malignancies section of the Pediatric Oncology Branch at the National Cancer Institute (NCI).

The most recent results presented at this year's annual meeting of the American Society of Clinical Oncology support earlier efficacy data, she noted. In the longest follow-up to date, researchers reported remissions lasting over 9 years in patients with relapsed/refractory B-cell lymphoma or CLL treated with Kite's axicaptagene cilleucel (Yescarta), one of two anti-CD19-directed CAR T-cell therapies approved by the FDA in 2017 (the other is Novartis' tisagenlecleucel [Kymriah]).

This study included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved in 54% of patients, and 22% had partial remission.

The other focus is long-term safety. Although some of the long-term adverse effects are known and are manageable, others fall into the theoretical realm. In early May 2020, the NCI held a multidisciplinary virtual conference on CAR T-cell therapy "to encourage collaborative research about the subacute and potentially long-term toxicity profile of these treatments."

"We know just a little at this point about late- and long-term effects of CAR-T therapy, because we are relatively early in the era of CAR T cells," said Merav Bar, MD, from the Fred Hutchinson Cancer Research Center in Seattle, Washington.

What is known is that B-cell aplasia represents the most common long-term adverse effect of CAR T-cell therapy. B-cell aplasia results when anti-CD19 CAR-T therapy wipes out healthy B cells as well as the malignant ones responsible for leukemia/lymphoma.

As major players in the immune system, B cells are a key defense against viruses. So B-cell aplasia represents a very specific type of immunosuppression. It is generally less severe than immunosuppression that occurs after organ transplant, which hits the immune system pretty much across the board and carries a much higher risk for infection.

The main concern is what happens when someone with B-cell aplasia encounters a new pathogen, such as SARS-CoV-2.

After infection, B cells generate memory cells, which are not killed off by anti-CD19 therapy and that stick around for life. So a patient such as Olson would still make antibodies that fight infections they experienced before receiving CAR-T therapy, such as childhood chickenpox. But now they are unable to make new memory cells, so these patients receive monthly immunoglobulin infusions to protect against pathogens they have not previously encountered.

Olson takes this in stride and says he isn't overly worried about COVID-19. He follows the recommended precautions for a man his age. He wears a mask, washes his hands frequently, and tries to maintain social distancing. But he doesn't stay locked up in his New Hampshire home.

"I took the attitude when I was diagnosed with cancer that I'm going to live my life," he said. "Quality of life to me is more important than quantity."

Another problem is the possibility of neuropsychiatric toxicity. Past studies have reported a wide range of such toxicities associated with CAR T-cell therapy, including seizures and hallucinations. Most have occurred early in the course of treatment and appear to be short-lived and reversible. However, there remain questions about long-term neuropsychiatric problems.

In a long-term study of 40 patients with relapsed/refractory CLL, non-Hodgkin lymphoma, and ALL, nearly half of patients (47.5%, 19/40) self-reported at least one clinically meaningful negative neuropsychiatric outcome (anxiety, depression, or cognitive difficulty) 1 to 5 years after anti-CD19 CAR T-cell therapy. In addition, 37.5% (15/40) self-reported cognitive difficulties.

"Patients with more severe neurotoxicity showed a trend for more cognitive difficulties afterwards," said Bar, senior author of the study.

However, teasing out the role that CAR T-cell therapy plays in these problems poses a challenge. All of these patients had been heavily pretreated with previous cancer therapy, which has also been associated with neuropsychiatric problems.

"So far, we don't know what caused it," Bar said. "Nevertheless, people need to pay attention to neuropsychiatric symptoms in CAR T-cell therapy. It is important to continue to monitor these patients for these issues."

Another potential problem is graft-vs-host disease (GVHD). This is not uncommon after hematopoietic stem cell transplants. It develops when the donor T cells view antigens on healthy recipient cells as foreign and attack them.

For patients who are treated with CAR T cells, GVHD is mostly a concern among individuals who have previously had a transplant and who are already at increased risk for it.

In a study of late effects among 86 adults treated with anti-CD19 CAR T cells for relapsed/refractory non-Hodgkin lymphoma, Bar and colleagues found that GVHD occurred only among patients who had received a previous donor stem cell transplant. Of these, 20% (3/15) developed GVHD about 28 months after CAR-T therapy.

"The data for CAR T cells causing GVHD really hasn't shown that it's a huge problem, although we have seen it and are continuing to monitor for it," the NCI's Shah commented to Medscape Medical News.

A range of other long-term adverse effects have been reported with CAR-T therapy, including prolonged cytopenias (reduced mature blood cells), myelodysplasia (bone marrow failure), and second malignancies.

In the study with the longest follow-up to date, 16% (7/43) of patients developed second malignancies, which is comparable to data from Bar's study in Seattle (15%, 13/86). The researchers in this study consider this rate to be no higher than expected: these patients had already received extensive chemotherapy, which increases the risk for other cancers, they point out.

However, this brings up theoretical concerns about the long-term effects of gene modification. CAR T cells are engineered using retroviruses (mainly lentiviruses), which randomly insert the CAR genes into the host genome. Doing so may cause mutations that could promote cancer. These lentiviruses also carry the theoretical risk of becoming capable of viral replication once inside the body.

To address these concerns, viruses used to engineer CAR T cells go through comprehensive safety testing. After therapy, patients are checked every few months during the first year and annually after that.

So far, there have been no reports of cancers associated with CAR T-cell therapy.

"Any type of cancer is a very theoretical risk," Bar told Medscape Medical News. "Most likely the malignancies in our study were related to prior treatment that the patients received. None of them had any evidence of replication-competent lentivirus, or any other evidence that the malignancies were related to the CAR T cells."

Another theoretical concern is the possibility of new-onset autoimmune disease, although, once again, no cases have been reported so far.

"We think of it as a theoretic possibility. Whenever you jack up the immune system, autoimmune disease is a potential risk," said Carl June, MD, director of the Center for Cellular Immunotherapies at the University of Pennsylvania.

June was the coprincipal investigator of the trial in which Olson participated. He is also the inventor on patents for CAR T cells licensed by the University of Pennsylvania to Novartis and Tmunity and is a scientific founder with equity in Tmunity.

Still, autoimmunity could occur, and scientists are looking out for it.

"We are continuing to be vigilant in our monitoring for autoimmune disease," Shah added. "We've been doing CAR T-cell therapy since 2012, and I think we have yet to see true autoimmunity beyond GVHD."

In the 10 years since Olson received CAR T-cell therapy, an entire industry has sprung up. Over 100 companies worldwide are now developing CAR T-cell therapies targeting various antigens. These therapies are directed at about 60 different tumor types, including solid tumors. Nearly 200 clinical trials are underway, though most are still in early stages: as of September 2019, only 5% had reached phase 3.

Clinical data show promising results for CAR T-cell therapy directed against CD22 (overexpressed on ALL cells), and BCMA (found on almost all multiple myeloma cells). Yet questions remain as to whether CAR T cells will be as effective if they target antigens other than CD19 or cells other than B lymphocytes. One of the biggest research questions is whether they will be effective against solid tumors.

One research avenue being watched with great interest is the development of universal CAR T cells. So far, such products are at very early stages of development (phase 1 trials), but they are attractive because of the potential advantages they offer over bespoke CAR T cells. Automating the process holds the promise of immediate availability, standardizing production, expanding access, and lowering costs. And because the T cells for this universal product come from healthy donors, they may function better than T cells that have been battered and bruised by past cancer treatments, or even the cancer itself.

However, precisely because they are developed from healthy donor T cells, universal CAR T cells may pose increased risk for GVHD. Scientists are trying to get around this problem by engineering universal CAR T cells that lack the T-cell receptor involved in GVHD.

There are also other concerns. Nature has a penchant for mutation. Engineering CAR T cells without T-cell receptors means the body may no longer detect or reject a universal CAR T cell if it goes rogue. Also, gene insertion in universal CAR-T therapy is targeted rather than random (as in bespoke CAR T cells), which could create off-target effects. Both issues create a theoretical risk of such products inducing an untreatable CAR T-cell therapyassociated cancer.

"The theoretic risk with universal cells is that their safety profile may not be as good for long term," June commented.

From that first trial in which June and Porter used CAR T cells, two of three patients they treated are still alive 10 years later.

Olson is one of these two, and he still undergoes monitoring every 3 months to check for relapse. So far, none of his tests have shown signs of his cancer returning.

After going into remission, Doug spent the next 6 to 9 months regaining his health and strength.

"I figured if I had this amazing treatment that saved my life, I had an obligation to stay alive," he said. "I'd better not die of something like a heart attack!"

He took up long distance running and has completed six half marathons. He became involved in the Leukemia and Lymphoma Society, participating in fund-raising and helping newly diagnosed patients. Over the years, he has also given talks for researchers, people with cancer, and healthcare providers.

Doug is now 73. Today, he marvels at how rapidly the CAR-T field has progressed.

"Twenty years ago, if you had cancer, your prospects weren't nearly as good as these days. In 2010, people still didn't believe in CAR T-cell therapy," he said. "My goal always in telling my story is a message of hope."

For more from Medscape Oncology, join us on Twitter and Facebook.

More here:
In Remission for 10 Years: Long-term Data on CAR-T Therapy - Medscape

MRFR predicts an Upsurge in the Leukemia Therapeutics Market valuation to USD 10.7 billion by 2023 – Jewish Life News

LeukemiaTherapeutics MarketOverview

The clinical condition an in which an increased number of abnormalleucocytesor generally called white blood cells of malignant characteristic is calledleukemia. Frequent infections, fever with chills and fatigue are early signs ofleukemia. Acute, chronic,lymphocytic, andmyelogenousleukemiasare classified underleukemia. Cancer statisticscenterof American Cancer Society estimates 61780 new cases ofleukemiain 2019. Treatment for such a malicious disease requires intense therapeutic attention. Therefore, the need for accurate treatment in the rising population ofleukemiapatients is the major factor impelling the globalleukemiatherapeutics market growth. The traditional therapies involved in the treatment ofleukemiaare chemotherapy, biological therapy, targeted therapy, radiation therapy, and stem cell transplant. The complex pathology ofleukemiademands advancements in medical infrastructure for treatment. Hence, letting the market key players immense opportunity to invest in research and development and bring forth innovation in theleukemiatherapy. This generates a lead for clinical researchers to investigate better drug administration methods. Efforts which are being made to deliver more effectiveleukemiatherapies is likely to trigger theleukemiatherapeutics market growth.

Get a FREE Sample with Complete TOCByConsidering the COVID-19 impact on Global Market @https://www.marketresearchfuture.com/sample_request/7425

However, on the flip side, the high cost of existingleukemiatherapies and investment required for developing new therapies is curbing theleukemiatherapeutics market expansion.

Globalleukemiatherapeutics market is expected to grow significantly over the forecast period. It is anticipated that the market held the value of USD 10.7 billion in 2017 and is projected to grow at a CAGR of 5.3% during the assessment period predicts Market Research Future (MRFR).

LeukemiaTherapeutics MarketSegmentalAnalysis

The globalleukemiatherapeutics market has been segmented into type, applications, and region.

Based on type, theleukemiatherapeutics market is segmented into chemotherapy, biological therapy, targeted therapy, radiation therapy, and stem cell transplant. The Chemotherapy segment which is anticipated to grow with the highest CAGR is further sub-segmented intoalkylatingagents,antimetabolites,antitumorantibiotics, and others.

Based on applications, theleukemiatherapeutics market is segmented into acutelymphocyticleukemia, acutemyelogenousleukemia, chroniclymphocyticleukemia, chronicmyelogenousleukemia, and others.

Based on region theleukemia therapeutics marketis segmented into North America, Europe, Asia-Pacific, and the Middle East & Africa. The Europeanleukemiatherapeutics market has been segmented into Western Europe and Eastern Europe. The Western Europe segment is further divided into Germany, France, the UK, Italy, Spain, and the rest of Western Europe. Theleukemiatherapeutics market in Asia-Pacific has been further divided into Japan, China, India, South Korea, Australia, and the rest of Asia-Pacific.

LeukemiaTherapeutics MarketRegional analysis

Reputed companies in North America manufacturing innovative and effective leukemic therapeutics is anticipated to bea majorforce allowing North America to dominate theleukemiatherapeutics market Growing numbers ofleukemiapatients in the European region is likely to drive theleukemiatherapeutics market in Europe in the upcoming years. Where theleukemiatherapeutics market in the Asia-Pacific region is likely to grow at a rapid rate, the Middle East & Africa is expected to show stagnancy in the market proliferation.

LeukemiaTherapeutics Industry Update

April 2019: Innovative Cellular Therapeutics (ICT), a clinical stage biotechnology company has achieved promisingpreclinicaland clinical results in late-stageleukemiaand lymphoma with novel CAR-T constructs. ICTCAR003, targets CD19 for the treatment of B-cell acutelymphoblasticleukemia.

Obtain Premium Research Report Details, Considering the impact of COVID-19 @https://www.marketresearchfuture.com/reports/leukemia-therapeutics-market-7425

About Market Research Future:

AtMarket Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half-Cooked Research Reports (HCRR), Raw Research Reports (3R), Continuous-Feed Research (CFR), and Market Research & Consulting Services.

MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients. Our market research studies by Components, Application, Logistics and market players for global, regional, and country level market segments, enable our clients to see more, know more, and do more, which help to answer all their most important questions.

In order to stay updated with technology and work process of the industry, MRFR often plans & conducts meet with the industry experts and industrial visits for its research analyst members.

Contact:

Akash Anand

Market Research Future

+1 646 845 9312

Email:[emailprotected]

NOTE: Our team of researchers are studying Covid-19 and its impact on various industry verticals and wherever required we will be considering covid-19 footprints for a better analysis of markets and industries. Cordially get in touch for more details.

Follow this link:
MRFR predicts an Upsurge in the Leukemia Therapeutics Market valuation to USD 10.7 billion by 2023 - Jewish Life News

Cannabis Found Effective to Treat Sickle Cell Disease Pain – The Weed Blog

Cannabis appears to be a safe and potentially effective treatment for the chronic pain that afflicts people with sickle cell disease, according to a new clinical trial co-led by University of California, Irvine (UCI) researcher Kalpna Gupta and Dr. Donald Abrams of UC San Francisco.

The studys results, released July 17, 2020, could have wide-reaching ramifications in that opioids are currently the primary treatment to ease the chronic and acute pain suffered by those afflicted with sickle cell disease (SCD).

SCD is a common inherited blood disorder, also called sickle cell anemia in its more serious stage. The disease affects an estimated 70,000 to 100,000 Americans.

The only cure for SCD is bone marrow or stem cell transplant, according to the Centers for Disease Control (CDC).

The rise in opioid-related deaths and addiction has prompted physicians to prescribe them less frequently, thereby leaving sickle cell patients with fewer and fewer treatment options.

These trial results show that vaporized cannabis appears to be generally safe, researcher Kalpna Gupt, a professor of medicine on the faculty of University of California Irvines Center for the Study of Cannabis.

Gupta said that, in addition to the study at hand, the trial opened the door for testing different forms of medical cannabis to treat chronic pain, including vaporized forms, which is what they used in the study. He noted that treating pain is the top reason people cite for seeking cannabis from dispensaries.

They [the trials] also suggest that sickle cell patients may be able to mitigate their pain with cannabis and that cannabis might help society address the public health crisis related to opioids. Of course, we still need larger studies with more participants to give us a better picture of how cannabis could benefit people with chronic pain.

The double-blind, placebo-controlled, randomized trial was the first to employ such gold-standard methods to assess cannabiss potential for pain alleviation in people with sickle cell disease, noted a press release from UCIs Center for the Study of Cannabis.

Researchers assessed participants pain levels throughout the treatment period and found that the effectiveness of cannabis, which contained equal parts THC and CBD, appeared to increase over time.

As the five-day study period progressed, the twenty three subjects reported that pain interfered less and less with their activities, including walking and sleeping, and there was a statistically significant drop in how much pain affected their mood.

The findings appear in JAMA Network Open.

Excerpt from:
Cannabis Found Effective to Treat Sickle Cell Disease Pain - The Weed Blog

End of Palestinian Authority coordination with Israel in response to annexation threat: decision already impacting medical referrals – occupied…

On 19 May 2020, Palestinian President Mahmoud Abbas announced that the Palestinian Authority (PA) considered itself absolved of all agreements and understandings it has signed with Israel and the United States. This decision was in response to Israels announcement of its intention to annex parts of the West Bank as early as 1 July, subject to the full agreement of the current U.S. administration. The threat of annexation has been widely condemned by the international community and the UN Secretary-General has stated that annexation would constitute a most serious violation of international law, grievously harm the prospect of a two-State solution and undercut the possibilities of a renewal of negotiations.

The PA has subsequently halted almost all bilateral contacts with Israel, including security coordination.[1] The PA has also stopped accepting the clearance revenues that Israel collects on its behalf which, adding to the economic uncertainty caused by the COVID-19 pandemic, has resulted in a loss of about 80 per cent of its monthly revenues, and is limiting its capacity to pay employees salaries.

The suspension of coordination has already affected humanitarian operations across the occupied Palestinian territory (oPt), including preparedness and response to the COVID-19 pandemic. Since the beginning of June, the import of essential supplies by humanitarian agencies has been disrupted, affecting some of the major operational organizations, including the World Health Organization (WHO), the UN Childrens Fund (UNICEF), and the UN Development Programme (UNDP), in addition to some NGOs.

This Humanitarian Bulletin article, the first in a series addressing the implications of the halt in coordination between the PA and Israel, focuses on the access of Palestinian patients, in particular from the Gaza Strip, to health care in East Jerusalem and in Israel; two Gaza infants have died thus far, before their transfers to hospitals in Israel and in East Jerusalem, respectively, could be arranged.

Access to essential health care critically affected

Information and cases included in this section were provided by the World Health Organization (WHO)

Many Palestinian patients throughout the oPt, and their companions, require Israeli-issued permits to access essential health services unavailable in their locality. For residents of the Gaza Strip, permits are required to access hospitals in the West Bank, including East Jerusalem, as well as Israel and Jordan. In the West Bank, patients and their companions also require permits to enter East Jerusalem, Israel or Jordan.[2] In 2019 each month, there were more than 7,000 patient permit applications from the West Bank (outside East Jerusalem), and over 2,000 from Gaza. Almost a third of applications are for persons with cancer. Approximately half of all referrals by the Palestinian Ministry of Health (MoH) were to hospitals in East Jerusalem.

Despite the cessation of permits coordination, patients and their families from the West Bank have been able to go in person to the Israeli District Coordination Office (DCO) to apply directly for permits. Additionally, the Israeli authorities are promoting a new mobile phone application, which Palestinians can download to apply for permits remotely, although concerns remain regarding the privacy and security implications of this system. Since the halt of coordination, there is no oversight of the application process for patients and companions, with limited means to track or record the number of those who apply; how many permits are denied or delayed; or to facilitate appeals on behalf of applicants.

In Gaza, although financial approvals for patient referrals are still issued, the PA has ended its coordination of permits requests for residents, including for patients and their companions. The issuance of referrals had already declined since the outbreak of COVID-19 in the oPt in March, following the Palestinian MoHs decision to reduce health services delivery in order to decrease transmission risk. This included efforts to localize some essential services, such as the short-term provision of limited chemotherapy through private providers in Gaza. In addition to the limitations imposed by the Palestinian authorities, the Israeli authorities further restricted eligibility criteria for exit permits, limiting those only to cancer patients and emergency cases.[3] Consequently, in March, patient exits declined to 1,279, from a monthly average of 1,777 in January and February. April recorded only 159 applications, of which 113 were approved, and May, 160 applications, of which 105 were approved.

While restrictions eased after an initial decline in COVID-19 cases, the recent increase of cases in the West Bank and Israel may cause authorities to extend the limitations on exit from Gaza to prevent the occurrence of a community outbreak there.

The exit of a limited number of emergency cases had been facilitated through the intercession of the Palestinian Centre for Human Rights (PCHR), a Gaza-based NGO, among other organizations. Selma, a 64-year-old with Hodgkins Lymphoma, was referred to a West Bank hospital for self-stem cell transplant, a procedure unavailable in Gaza. With the help of PCHR, she obtained a permit to travel to the West Bank on 7 June, the day of her scheduled transplant operation. However, PCHR ended the facilitation of coordination of permits on 9 June, following an Israeli media report portraying the organization role as replacing the PAs role.[4] Currently, a number of civil society organizations and hospitals are coordinating for patients referred for urgent treatment.

Osama, a one-year-old boy from Gaza City, was diagnosed with leukaemia on 8 June and referred urgently to Augusta Victoria Hospital in East Jerusalem for immediate treatment. Through the considerable efforts of hospital staff, he received a permit on 11 June, and he was able to travel to the hospital the same day.

Although Osamas mother was still breastfeeding him, he was accompanied by his grandmother on the grounds that older people find it easier to pass the security conditions required for permits. The medical team at Augusta Victoria Hospital reported his severe distress for days after his separation from his mother. Osamas father commented, We were told he is crying most of the time. Someone from the hospital has contacted me to try to coordinate a permit for Osamas mother to travel and be close to him, but we are still waiting.

The first fatality in Gaza following the halt in coordination was reported on 18 June, when eight-month-old Omar Yaghi, died of cardiac complications, before he was able to receive a permit to travel for an operation to Sheba Medical Center in Israel. On 22 June, a nine-day-old infant, Anwar Harb, who also suffered from heart problems, died before he could receive treatment in East Jerusalem. The Israeli authorities had agreed to his transfer to Al-Makassed Hospital that day, but the hospital was unable to coordinate the ambulance transfer in time.[5]

Following the death of Omar Yaghi, a coalition of Israeli-based organizations sent an urgent letter to the Israeli Defence Minister, Attorney General, and the head of COGAT, demanding that Israel, as the occupying power, immediately ensure Palestinian travel through the Erez Crossing. The organizations specifically requested that Israel remove all bureaucratic restrictions on the submission of permit applications by patients and other humanitarian cases and allow Gaza residents to enter Israel and the West Bank immediately; immediately clarify how travel permit applications may be filed by Gaza residents; and publish clear, detailed, and accessible information about the alternative application procedure.

Roles and responsibilities of the parties

There have been suggestions that international organizations, particularly the UN, may be requested to perform the coordination activities, which the PA has been previous responsible for. However, as stated by UN Special Coordinator, Nikolay Mladenov, in his most recent briefing to the UN Security Council; while the UN is prepared to provide support on an emergency basis, the UN cannot replace the Palestinian Authority. It is critical that humanitarian and other assistance not be delayed or stopped.

The emergency support to be provided by the UN does not absolve Israel or the PA of their primary obligations towards the Palestinian population in the oPt. Under international law, Israel, as occupying power, bears the primary responsibility for the protection and welfare of this population, including access to essential health services. Even prior to the suspension of coordination, Palestinian patients, and their companions, faced major barriers to timely access to essential healthcare, due to delays and denials of the Israeli-issued permits needed for access to major specialist centres in East Jerusalem and in Israel.

The PA, having ratified human rights treaties, also has certain duties towards this population, within the limits of its control, as does the de facto authority in the Gaza Strip. These include ensuring respect and protection for the right to the highest attainable standard of health, and ensuring that policies introduced, or the withdrawal from previous responsibilities, do not cause harm.

Based on these considerations, the UN has agreed with both the Palestinian and Israeli authorities the establishment of a temporary mechanism, as part of which the UN will facilitate the transfer of the required documentation between the sides, to ensure access for Gaza patients to essential health services in the West Bank, including East Jerusalem, and Israel. This mechanism is expected to start operating during the second half of July.

[1] The only exception is coordination relating to the Kerem Shalom crossing for goods in and out of Gaza, which continues to operate as before.

[2] The majority of men over 55 years of age, and women over 50 from the remainder of the West Bank, as well as children 13 years and under, and accompanied by an adult, do not require permits to enter Israel or East Jerusalem.

[3] https://www.ochaopt.org/content/additional-treatment-option-available-ca...

[4] See https://www.pchrgaza.org/en/?m=20200609

[5] http://www.alhaq.org/cached_uploads/download/2020/06/27/200626-joint-urg...

Go here to read the rest:
End of Palestinian Authority coordination with Israel in response to annexation threat: decision already impacting medical referrals - occupied...

Addiction Treatment Market Survey Report 2020 Stats and Forecasts to 2026 – Cole of Duty

AMA Research added a comprehensive research document of 200+ pages on Addiction Treatment market with detailed insights on growth factors and strategies. The study segments key regions that includes North America, Europe, Asia-Pacific with country level break-up and provide volume* and value related cross segmented information by each country. Some of the important players from a wide list of coverage used under bottom-up approach are Cipla Ltd. (India),Allergan plc (Ireland),Alkermes plc (Ireland),Pfizer Inc. (United States),Orexo AB (Sweden),GlaxoSmithKline plc (United Kingdom),Purdue Pharma L.P (United States),Mallinckrodt Pharmaceuticals (United Kingdom),Reckitt Benckiser (United Kingdom),Teva Pharmaceuticals (Israel)

Request a sample report @ https://www.advancemarketanalytics.com/sample-report/51501-global-addiction-treatment-market

Over the past couple of decades drugs, alcohol, as well as smoking, has led to upsurge the menace of the drugs. In addition to this, increasing government concerns regarding the esclating problem of addiction and introduction to addition curing drugs have escalated the demand for the addiction treatments. These treatments can be carried out in different settings such as medication and behavioral therapies. Drug or alcohol addiction may mostly cause chronic disorder characterized by occasional relapses, thus, a single treatment might not be enough. The patients might require a series of treatments for a longer time span which will further increase the need for addiction treatments.

Market Segmentation & Scope:

Study by Type (Alcohol Addiction Treatment, Tobacco/Nicotine Addiction Treatment, Opioid Addiction Treatment, Other Substance Addiction Treatment), Drug Type (Bupropion, Varenicline, Acamprosate, Disulfiram, Naltrexone, Methadone, Buprenorphine, Nicotine Replacement Products), Treatment Center (Outpatient Treatment Center, Residential Treatment Center, Inpatient Treatment Center), Distribution Channel (Hospital, Pharmacies, Medical Stores)

Avail 30-50% Discount on various license type on immediate purchase @ https://www.advancemarketanalytics.com/request-discount/51501-global-addiction-treatment-market

A View on Influencing Trends:

Introduction to Addiction Treatment Drugs with Minimal Side Effects

Growing Demand for Nicotine Addiction Treatments especially Nicotine Gums

Growth Drivers in Limelight: Assistance to Voluntary Organizations for Prevention of Alcoholism and Drug Abuse

Financial Assistance in the Field of Social Defence

Major Roadblocks Worthy Attention: Rising Instances of Misleading Sales Tactics, Deceptive Advertising, and Unethical Marketing Practices

Highly Unregulated Sector of Drug Rehab Vulnerable to many Patients

Check Complete Table of Content @ Table of Content @ https://www.advancemarketanalytics.com/reports/51501-global-addiction-treatment-market

Country level Break-up includes:

North America (United States, Canada and Mexico)

Europe (Germany, France, United Kingdom, Spain, Italy, Netherlands, Switzerland, Nordic, Others)

Asia-Pacific (Japan, China, Australia, India, Taiwan, South Korea, Middle East & Africa, Others)

Strategic Points Covered in Table of Content of Global Addiction Treatment Market:

Chapter 1: Introduction, market driving force product Objective of Study and Research Scope the Addiction Treatment market

Chapter 2: Exclusive Summary the basic information of the Addiction Treatment Market.

Chapter 3: Displaying the Market Dynamics- Drivers, Trends and Challenges of the Addiction Treatment

Chapter 4: Presenting the Addiction Treatment Market Factor Analysis Porters Five Forces, Supply/Value Chain, PESTEL analysis, Market Entropy, Patent/Trademark Analysis.

Chapter 5: Displaying market size by Type, End User and Region 2014-2019

Chapter 6: Evaluating the leading manufacturers of the Addiction Treatment market which consists of its Competitive Landscape, Peer Group Analysis, BCG Matrix & Company Profile

Chapter 7: To evaluate the market by segments, by countries and by manufacturers with revenue share and sales by key countries (2020-2025).

Chapter 8 & 9: Displaying the Appendix, Methodology and Data Source

Finally, Addiction Treatment Market is a valuable source of guidance for individuals and companies in decision framework.

What benefits does AMA research study is going to provide?

Definitively, this report will give you an unmistakable perspective on every single reality of the market without a need to allude to some other research report or an information source. Our report will give all of you the realities about the past, present, and eventual fate of the concerned Market.

Thanks for reading this article; you can also get individual chapter wise section or region wise report version like North America, Europe or Southeast Asia.

Buy full version of this report @ https://www.advancemarketanalytics.com/buy-now?format=1&report=51501

Contact Us:

CRAIG FRANCIS (PR & Marketing Manager)

[emailprotected]

Ph: +1 (206) 317 1218

More here:
Addiction Treatment Market Survey Report 2020 Stats and Forecasts to 2026 - Cole of Duty

13 Promising Covid Treatments Emerging from Israel – The Jewish Voice

In parallel to vaccine research, theres an urgent need for effective treatments for the respiratory disease caused by the SARS-CoV-2 coronavirus.

By: Abigail Klein Leichman

Scientists across the globe are working on vaccines to prevent Covid-19 infection.

But in the meanwhile, and even after initial vaccines are approved, there is an urgent need for effective treatments for the respiratory disease caused by the SARS-CoV-2 coronavirus.

Most potential treatments target the life-threatening lung inflammation typical of serious Covid-19 cases. Its caused by a phenomenon called a cytokine storm.

Cytokines are proteins that trigger inflammation as a natural response to infection. In response to a virus overload, in this case in the lungs, the immune system activates a storm of cytokines. Too many cytokines lead to too much inflammation, which can damage the lungs and cause respiratory distress.

Israeli hospitals were among the first anywhere to use dexamethasone, a steroid drug, to stop cytokines storms and reduce lung inflammation in severely ill Covid-19 patients. However, steroids can suppress the immune response too strongly.

Additionally, an Israeli hospital is among the first to do a randomized, double-blind, placebo-controlled clinical trial of ivermectin, a drug to treat parasitic infections in people and animals, to see if it can shorten the duration of the disease if given to Covid-19 patients immediately after diagnosis.

Israelis are also formulating novel therapeutics of their own.

Below we summarize 13 potential Israeli treatments using a variety of approaches such as placenta-derived cells, peptides, blood plasma of recovered patients, and the cannabis compound CBD.

There is plenty of room for more than one treatment.

We believe humanity needs a toolbox of different solutions for Covid-19, says Immanuel Lerner, CEO of Pepticom, one of the companies detailed below.

Pluristem

On June 11, Pluristem Therapeutics of Haifa announced a multicenter Phase 2 US Food and Drug Administration (FDA) efficacy and safety study of its PLX-PAD cells for treating severe Covid-19 complicated by acute respiratory distress syndrome (ARDS).

PLX, an injected regenerative placenta-derived cell therapy, stimulates the immune systems natural regulatory T cells and M2 macrophages, possibly preventing or reversing a cytokine storm. PLX cells potentially reduce the incidence and/or severity of Covid-19 pneumonia and pneumonitis.

Pluristem has treated Covid-19 patients under compassionate use programs in the United States and Israel. Initial data from 18 patients showed that 75% were off mechanical ventilation within 28 days.

PLX cells are available off-the-shelf and once commercialized, can be manufactured in large-scale quantities, offering a key advantage in addressing a global pandemic, the company said.

Silkim

Jerusalem-based Silkim Pharma recently submitted Coronzot, its novel treatment for Covid-19 patients with moderate to severe symptoms, to the FDAs Investigational New Drug (IND) program.

IND designation would give Silkim permission to start human clinical trials and to ship Coronzot across state lines before a marketing application has been approved.

Coronzots novel mechanism targets a pivotal factor in cytokine storms. It removes an inflammatory overaccumulation of labile iron and replaces it with a minute amount of gallium or zinc.

This not only suppresses the storm but also inhibits viral proteins that attack the lungs and heart. Gallium inhibits virus replication and promotes apoptosis (self-destruction) of already invaded cells. Zinc helps suppress inflammatory reactions and enzymes that enable coronavirus replication.

The company is actively engaged in the FDA process. We look forward to finalizing the IND and then moving towards conducting clinical studies of Coronzot for Covid-19, said Silkim Pharma CEO Dror Chevion.

RedHill Biopharma

RedHill Biopharma, based in Raleigh, North Carolina and Tel Aviv, is moving rapidly to advance our development program with opaganib for Covid-19, according to a June 10 statement by Dr. Mark L. Levitt, RedHill medical director.

RedHill acquired opaganib from US-based Apogee Biotechnology, which developed this oral drug to fight cancer, inflammation and viruses.

RedHill has seen encouraging preliminary findings from six Israeli Covid-19 patients given opaganib under compassionate use to reduce lung inflammation. All were weaned from supplemental oxygen and discharged from the hospital without having to receive mechanical ventilation.

RedHill plans a multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 clinical study on 270 US patients with severe Covid-19 pneumonia.

We are expanding the development program to Russia and additional European countries, in parallel with the US clinical study, in order to accelerate the collection of robust data on the potential efficacy of opaganib against Covid-19, said Levitt.

The company is working with government agencies worldwide to allow more patients access to the investigational drug through clinical studies and compassionate use programs.

InnoCan

InnoCan Pharma Israel and Tel Aviv University tech-transfer company Ramot are collaborating to develop a new CBD-loaded exosome technology to fight lung inflammation.

Exosomes, small particles created from stem cells, can act as homing missiles targeting specific damaged organs and facilitating cell-to-cell communication.

Combining the cell-healing properties of exosomes with the anti-inflammatory properties of the cannabis-derived compound CBD is expected to have a strong synergetic effect. The treatment is administrated by inhalation.

Stero Biotechs

Stero Biotechs of Bnei Brak has started a small clinical trial at Rabin Medical Center in Petah Tikva on the tolerability, safety and efficacy of a CBD-enhanced steroid treatment for hospitalized Covid-19 patients.

Steroid treatment is usually the first or second line of treatment for hospitalized patients. CBD enhances the therapeutic effect of steroid treatment and treats the bio-mechanism affected by the virus, the company explained.

Eybna and CannaSoul

Two Israeli cannabis R&D firms, Eybna Technologies and CannaSoul Analytics, are developing a proprietary terpene formulation for modulating cytokine storms.

Terpenes are organic compounds found in cannabis and other plants. Studies suggest they can be effective antiviral agents.

CannaSouls Cytokine Storm Assay (from its Myplant-Bio subsidiary) will aid in optimizing and customizing Eybnas novel NT-VRL inhaled formulation for treatment and prevention of viral infections in high-risk populations and actively ill patients.

The FDA considers this assay as a good predictor for cytokine storm response and immunotoxicity, and it is commonly required in the development of biological treatments, according to CannaSoul Chairman and CSO Prof. Dedi Meiri.

The NT-VRL formulation intended to be used via inhalation, said Eybna CEO Nadav Eyal. This delivery method dramatically increases the terpenes bioavailability by directly contacting the infected cells in the respiratory system.

CannaSoul aims to identify other cannabis molecules capable of suppressing a cytokine storm in response to Covid-19 without completely suppressing the immune system. It is also studying how cannabis molecules could modulate the ACE2 receptor, which allows the virus to inject its genetic expression into human cells.

Kamada

Based in Rehovot, Kamada has begun supplying its experimental plasma-derived Hyperimmune IgG therapy for compassionate use in severe Covid-19 cases in Israel.

The treatment is based on plasma donated by recovered Israeli Covid-19 patients. One critically ill patient at Hadassah Medical Center showed initial improvement after having the experimental IgG therapy but ultimately did not survive.

During the third quarter of this year, Kamada expects to start a Phase 1/2 clinical study in hospitalized Covid-19 patients in Israel and hold a pre-IND meeting with the FDA to expand clinical development in the United States in partnership with Kedrion Biopharma.

Kedrion is collecting plasma from recovered American Covid-19 patients at 23 FDA-approved centers across the United States. This will be used by Kamada to manufacture additional batches of the product.

To the best of our knowledge, Kamada is the first company globally to complete manufacturing of a plasma-derived IgG product for the treatment of Covid-19, said Kamada CEO Amir London.

Israel Institute for Biological Research

The government-run Israel Institute for Biological Research (IIBR) announced in May that analogues of two drugs for Gauchers disease proved effective against SARS-CoV-2.

This drug cocktail is made up of the FDA-approved Cerdelga and an analogue of a second drug in advanced stages of the approval process.

The IIBR study on cell cultures demonstrated that the two-drug treatment significantly reduced the replication capacity of the coronavirus and the destruction of the infected cell. This potential treatment is currently being tested in animals infected with the coronavirus.

The IIRB also isolated several key coronavirus antibodies that successfully neutralized aggressive coronavirus in lab tests. These could form the basis of a future treatment following further testing.

Pepticom

Based in Jerusalem, Pepticom computationally designs novel peptide drug candidates using artificial intelligence. The company raised $5 million last year.

Three months ago, Pepticom began implementing its proprietary AI technology on various coronavirus proteins to identify novel peptides that inhibit interaction between the spike protein of SARS-Cov-2 and the ACE2 receptor thereby stopping the virus from entering the cell.

CEO Immanuel Lerner says three such proteins have already been identified and are being validated in the lab.

Using AI is a fast way to find these peptides, which are less expensive and easier to produce than antibodies, Lerner tells ISRAEL21c. Many parties are interested in looking at our results and finding ways to develop this further.

Bonus BioGroup

In April, Bonus BioGroup initiated a preclinical study of MesenCure, its unique drug for treating acute and life-threatening respiratory distress in coronavirus and pneumonia patients.

MesenCure consists of activated mesenchymal stromal (stem) cells from healthy adult donors. The activation of these MSCs is intended to boost their ability to reduce lung inflammation, promote regeneration of the diseased lung tissue, and alleviate respiratory and other symptoms in the lungs.

The development of MesenCure relies on more than a decade of related experience and technologies that Bonus BioGroup has used in developing its lead product, a tissue-engineered bone graft also based on MSCs.

With the current coronavirus outbreak, Bonus BioGroup has started tissue culture studies into the potential of these MSCs, further activated, to alleviate inflammation, including in the lungs, and possibly attenuate the cytokine storm in COVID-19 patients, the company explained.

The preclinical study in several animal models is expected to be completed in the third quarter of 2020. The company said preliminary results indicate that following the treatment with MesenCure, the microscopic appearance of the treated lungs was similar to a healthy lung, and a significant improvement in additional related parameters was achieved.

Bonus BioGroup presented these results to 1,800 scientists, physicians, and public opinion leaders at the virtual conference of the International Society for Cell & Gene Therapy in May.

NanoGhost

Technion-Israel Institute of Technology Prof. Marcelle Machluf developed a drug-delivery technology that uses reconstructed mesenchymal stem cells as nano-vesicles to transport medicine directly to a target.

NanoGhost is the startup she established to commercialize the technology, which has proven successful in treating pancreatic, lung, breast, prostate, and brain cancer in mice. The NanoGhost technology has been patented in the United States and Europe, with additional patents pending in India and China.

Now, Machluf is adapting her technology to create decoy NanoGhosts that attract and entrap the coronavirus, making for a less severe infection. She explains it in the video below.

Enlivex

Enlivex Therapeutics of Ness Ziona is developing Allocetra, a novel immunotherapy medication to treat organ dysfunction and acute multiple organ failure associated with sepsis and Covid-19, as well as solid tumors.

Allocetra rebalances a severely unbalanced immune system by engaging with the immune systems own regulation mechanisms. It is designed to restore safe immune balance following a cytokine storm.

Enlivex is starting to recruit Covid-19 patients in Israel and in the United States to test the potential effect of Allocetra on moderate to severe cases. A patent from the Japan Patent Office is expected during the third quarter of 2020.

Weizmann Institute of Science

Organic chemist Nir London of the Weizmann Institute of Science in Rehovot is co-leading a collaborative project to identify small molecules that can bind to and inhibit a protease enzyme that the SARS-CoV-2 virus needs to reproduce.

London and his research team had previously developed an advanced method for identifying potential inhibitors for numerous proteins.

So far, we have made close to 800 compounds and tested more than 650 and keep getting closer to sufficiently potent inhibitors, London tells ISRAEL21c.

These inhibitors will be further investigated for their potential as a starting point for new drugs against the coronavirus.

London is working with researchers from Oxford University, Memorial Sloan Kettering Cancer Center, University of British Columbia, and Californian-based biotech company.

(Israel 21C)

Read more:
13 Promising Covid Treatments Emerging from Israel - The Jewish Voice

New Clues from Fruit Flies about the Critical Role of Sex Hormones in Stem Cell Control – Newswise

Newswise In one of the first studies addressing the role of sex hormones impact on stem cells in the gut, scientists outline new insights showing how a steroidal sex hormone, that is structurally and functionally similar to human steroid hormones, drastically alters the way intestinal stem cells behave, ultimately affecting the overarching structure and function of this critical organ. The authors found that ecdysone, a steroid hormone produced by fruit flies, stimulates intestinal stem cell growth and causes the gut of the female fruit fly to grow in size, and induces other critical changes. The study also provides a mechanism to account for sex-specific roles for intestinal stem cells in normal gut function. Moreover, the research presents evidence that gut hormones may accelerate tumor development. The findings, reported jointly by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) and the German Cancer Research Center (DKFZ), are published today in the journal Nature.

Bruce Edgar, PhD, a stem cell biologist at HCI and professor of oncological sciences at the U of U, together with Aurelio Teleman, PhD, division head at DKFZ and professor at Heidelberg University jointly led the work. They asked whether sex hormones affect intestinal stem cells ability to multiply and contribute to gut growth. My lab and many others around the world have studied the Drosophila gut for some time to better understand how stem cells are regulated, says Edgar. We knew that male and female fruit flies exhibited differences in their intestine for example, the females intestine is larger than the males, and females develop intestinal tumors much more readily than males but we didnt know why. This study adds significant insights into these differences, and how they arise.

The Edgar and Teleman teams found that ecdysone, a sex-specific hormone, can drastically alter the growth properties of stem cells in an organ that, remarkably, is not directly involved in reproduction. They found that these changes affect the structure and function of the entire organ. They discovered that subjecting male flies to ecdysone caused their otherwise slow dividing stem cells to divide as fast as in females, leading to intestinal growth in males as well. This suggests that the limiting difference between the division of stem cells in male and female flies is the circulating levels of the hormone.

This process confers both advantages and disadvantages to the female fruit fly during the course of its life. Initially, more ecdysone in females helps with the evolutionarily critical processes of reproduction. It promotes gut enlargement, facilitating nutrient absorption, which helps the fly lay more eggs. But later in life, the ecdysone hormone, produced by the ovaries, eventually causes gut disfunction that can shorten the lifespan in female fruit flies by creating an environment that favors tumor growth. While humans dont produce ecdysone, they do have related steroid hormones such as estrogen, progesterone and testosterone, which have similar mechanisms of action.

The experimental work on this study was performed primarily by Sara Ahmed, a joint PhD student between the Edgar and Teleman labs at the Zentrum fr Molekulare Biologie der Universitt Heidelberg (ZMBH) and the DKFZ. Ahmed designed experiments utilizing various genetic tools to switch genes on and off in different cell types in the flys intestine and in its ovaries, which produce ecdysone. Our study provides conclusive evidence that sex hormones alter the behavior of non-sex organs like the intestine, says Ahmed. She further speculates that long-term implications of this research may include exploration of new paths to treating human cancers.

According to the researchers, understanding whether a similar stem cell-hormone relationship operates in human organs will require further studies. They plan to explore this in the future. In addition to the critical role played by sex hormones in intestinal stem cell behavior, the authors believe this study in Drosophila potentially unveils a new mechanism that may play out in human physiology and pathology. Insights from this study add to a growing body of work showing that the incidence cancers of non-reproductive organs, including colon and gastric cancers, are different in males and females.

This study was supported by the National Institutes of Health including the National Cancer Institute P30 CA01420114, the National Institute of General Medical Sciences R01 124434, the European Research Council AdG268515, DKFZ, and Huntsman Cancer Foundation.

###

About Huntsman Cancer Institute at the University of Utah:Huntsman Cancer Institute (HCI) at the University of Utah is the official cancer center of Utah. The cancer campus includes a state-of-the-art cancer specialty hospital as well as two buildings dedicated to cancer research. HCI treats patients with all forms of cancer and is recognized among the best cancer hospitals in the country by U.S. News and World Report. As the only National Cancer Institute (NCI)-Designated Comprehensive Cancer Center in the Mountain West, HCI serves the largest geographic region in the country, drawing patients from Utah, Nevada, Idaho, Wyoming, and Montana. More genes for inherited cancers have been discovered at HCI than at any other cancer center in the world, including genes responsible for hereditary breast, ovarian, colon, head, and neck cancers, along with melanoma. HCI manages the Utah Population Database, the largest genetic database in the world, with information on more than 11 million people linked to genealogies, health records, and vital statistics. HCI was founded by Jon M. and Karen Huntsman.

About DKFZ: The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Wrttemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

See the article here:
New Clues from Fruit Flies about the Critical Role of Sex Hormones in Stem Cell Control - Newswise