Past, Present and Future: How Non-Clear Cell Kidney Cancer Has Evolved – Curetoday.com

Those with non-clear cell kidney cancer have much to look forward to as oncologists understanding of the disease is evolving.

BY Kristie L. Kahl

At A Vision of Hope: A Kidney Cancer Educational Symposium, which was hosted by the Judy Nicholson Kidney Cancer Symposium and Penn Medicine Abramson Cancer Center, Narayan discussed the past, present and future of the treatment of non-clear cell kidney cancer.

Non-clear cell kidney cancer accounts for 15% to 20% of kidney cancers and consists of papillary type 1 and 2, chromophobe and unclassified disease, as well as several additional less common subtypes. However, with all of these types, oncologists understanding of treatment for non-clear cell kidney cancer has evolved over the last several years, Narayan explained.

Where, instead of viewing this as a single uniform entity, we began to appreciate that this actually represents a spectrum of different diseases, all with distinctive molecular and genetic clinical courses and variable responses to treatment, he said.

In the past, most initial trials evaluated agents only for clear cell kidney cancer which comprises 80% of patients with little consensus on how to treat non-clear cell disease.

Two trials evaluated systemic treatments for non-clear cell kidney cancer the ESPN and ASPEN trials, both comparing Sutent (sunitinib) with Afinitor (everolimus). Although both drugs appeared effective in patients with clear cell kidney cancer, outcomes were merely modest for those with non-clear cell disease.

Moving forward to present day, oncologists began to think about the disease differently. We've begun to change our thinking in terms of how we think about non-clear cell kidney cancer. Instead of acting as lumpers, we begin to think (of the disease) more as splitters and recognize that this is truly a heterogeneous disease, Narayan said.

With this, oncologists began to think about their improved understanding of the molecular underpinnings of each subtype of the disease, and defined characteristics based on chromosomal alteration, tumor metabolism and more, he added.

As part of the Cancer Genome Atlas, a collaborative project to create comprehensive maps of the key genomic changes in different cancer types, oncologists were able to define pathways among each subtype.

There are areas of overlap with clear cell kidney cancer, but also some very important and unique differences with each of the subtypes of non-clear cell, Narayan explained. So as we start to think about how to use this information to improve the treatments for patients with non-clear cell disease, were really starting to have a change in the treatment paradigm. Instead of simply extrapolating treatments from clear cell kidney cancer, and testing them in non-clear cell patients, it would be ideal to have biology-driven clinical trials that assess specific treatments for specific subtypes.

He added that there are challenges with this ideology, however, because it is difficult to accrue patients in a trial for uncommon kidney cancers, but the benefit of having uniform biology to test the rationale for new treatment strategies could help.

Currently, researchers have evaluated Sutent, Cabometyx (cabozatinib), savolitinib (an experimental drug) and Xalkori (crizotinib) in patients with papillary renal cell carcinoma types 1 and 2. More recently, however, Sutent and Cabometyx have become the only two horses in the race, Narayan said.

In the future, he is hopeful that oncologists understanding of overlap and the differences seen with conventional clear cell kidney cancer will continue to evolve.

In thinking about the treatment of non-clear cell kidney cancer, especially as we move to the future, it's clear that our understanding of this disease is evolving, Narayan concluded. Our clinical trials will hopefully evaluate treatment strategies to target unique biology.

Continue reading here:
Past, Present and Future: How Non-Clear Cell Kidney Cancer Has Evolved - Curetoday.com

Study focuses on repair and reversal of damage caused by Huntington’s disease – UCLA Newsroom

UCLA research identifies a potential strategy that may lead to treatment for the disorder

UCLA

The image shows astrocytes (in purple) with mutant huntingtin protein inclusions (green). Some of these were located within astrocytes as shown in the expanded image on the right.

A new study examining the role that star-shaped brain cells called astrocytes play in Huntingtons disease has identified a potential strategy that may halt the disease and repair some of the damage it causes.

Astrocytes interact with and support neurons, or nerve cells, and other brain cells. Although astrocytes outnumber neurons, little is known about how they interact with synapses, the junctions between neurons that enable them to communicate and convey messages to each other.

The study, led by UCLA researchers and published in the journal Science Translational Medicine, found that Huntingtons disease damages astrocytes at the early stages of the disease, which contributes to the neuropsychiatric symptoms that develop as the disease progresses.

Huntingtons is caused by a mutation in the huntingtin gene. People with Huntingtons experience depression, irritability and other neurological and behavioral problems. They may also have difficulty processing information and controlling their bodys movements.

Its likely that we will not understand brain diseases without also understanding what happens to the cells that actually form the brain, including astrocytes, said Baljit Khakh, the studys lead investigator and a professor of physiology and neurobiology at the David Geffen School of Medicine at UCLA.

Khakh led a team that previouslypioneereda method that enables scientists to look inside thebrainsof mice to observe astrocytes influence over nerve-cell communication in real time. The scientists are able to see how interactions between synapses and astrocytes change over time, and as a result of neurological diseases.

For the recent study, researchers observed the progression of Huntingtons disease in samples from the brains of deceased humans, and in living mice that carry the gene mutation. They found that by suppressing the mutation in astrocytes, they were able to stop the disease progression in mice and repair some of the damage that can be seen when examining the cells closely.

We believe that if we are able to stop the progression of the disease in astrocytes and neurons, then we may be able to restore activity in the brain to what it was before the disease developed, Khakh said.

Study author Blanca Diaz-Castro, a former UCLA postdoctoral scholar, said that while its well-known that the mutation causes the cell death in neurons, this is the first study to identify how the mutation affects astrocytes.

We believe the findings will lead to further studies on astrocytes in brain diseases, she said.

The study also established a database that can now be used for future studies of astrocytes in many neurodegenerative diseases. Khakh said the findings add to a growing body of evidence that suggests impaired astrocytes play a role in many neurological diseases, such as Huntingtons, ALS, multiple sclerosis and Alzheimers.

View original post here:
Study focuses on repair and reversal of damage caused by Huntington's disease - UCLA Newsroom

Quantum dots that light up TVs could be used for brain research – The Conversation US

While many people love colorful photos of landscapes, flowers or rainbows, some biomedical researchers treasure vivid images on a much smaller scale as tiny as one-thousandth the width of a human hair.

To study the micro world and help advance medical knowledge and treatments, these scientists use fluorescent nano-sized particles.

Quantum dots are one type of nanoparticle, more commonly known for their use in TV screens. Theyre super tiny crystals that can transport electrons. When UV light hits these semiconducting particles, they can emit light of various colors.

That fluorescence allows scientists to use them to study hidden or otherwise cryptic parts of cells, organs and other structures.

Im part of a group of nanotechnology and neuroscience researchers at the University of Washington investigating how quantum dots behave in the brain.

Common brain diseases are estimated to cost the U.S. nearly US$800 billion annually. These diseases including Alzheimers disease and neurodevelopmental disorders are hard to diagnose or treat.

Nanoscale tools, such as quantum dots, that can capture the nuance in complicated cell activities hold promise as brain-imaging tools or drug delivery carriers for the brain. But because there are many reasons to be concerned about their use in medicine, mainly related to health and safety, its important to figure out more about how they work in biological systems.

Researchers first discovered quantum dots in the 1980s. These tiny particles are different from other crystals in that they can produce different colors depending on their size. They are so small that that they are sometimes called zero-dimensional or artificial atoms.

The most commonly known use of quantum dots nowadays may be TV screens. Samsung launched their QLED TVs in 2015, and a few other companies followed not long after. But scientists have been eyeing quantum dots for almost a decade. Because of their unique optical properties they can produce thousands of bright, sharp fluorescent colors scientists started using them as optical sensors or imaging probes, particularly in medical research.

Scientists have long used various dyes to tag cells, organs and other tissues to view the inner workings of the body, whether that be for diagnosis or for fundamental research.

The most common dyes have some significant problems. For one, their color often cannot survive very long in cells or tissues. They may fade in a matter of seconds or minutes. For some types of research, such as tracking cell behaviors or delivering drugs in the body, these organic dyes simply do not last long enough.

Quantum dots would solve those problems. They are very bright and fade very slowly. Their color can still stand out after a month. Moreover, they are too small to physically affect the movement of cells or molecules.

Those properties make quantum dots popular in medical research. Nowadays quantum dots are mainly used for high resolution 3D imaging of cells or molecules, or real-time tracking probes inside or outside of animal bodies that can last for an extended period.

But their use is still restricted to animal research, because scientists are concerned about their use in human beings. Quantum dots commonly contain cadmium, a heavy metal that is highly poisonous and carcinogenic. They may leak the toxic metal or form an unstable aggregate, causing cell death and inflammation. Some organs may tolerate a small amount of this, but the brain cannot withstand such injury.

My colleagues and I believe an important first step toward wider use of quantum dots in medicine is understanding how they behave in biological environments. That could help scientists design quantum dots suitable for medical research and diagnostics: When theyre injected into the body, they need to stay small particles, be not very toxic and able to target specific types of cells.

We looked at the stability, toxicity and cellular interactions of quantum dots in the developing brains of rats. We wrapped the tiny quantum dots in different chemical coats. Scientists believe these coats, with their various chemical properties, control the way quantum dots interact with the biological environment that surrounds them. Then we evaluated how quantum dots performed in three commonly used brain-related models: cell cultures, rat brain slices and individual live rats.

We found that different chemical coats give quantum dots different behaviors. Quantum dots with a polymer coat of polyethylene glycol (PEG) were the most promising. They are more stable and less toxic in the rat brain, and at a certain dose dont kill cells. It turns out that PEG-coated quantum dots activate a biological pathway that ramps up the production of a molecule that detoxifies metal. Its a protective mechanism embedded in the cells that happens to ward off injury by quantum dots.

Quantum dots are also eaten by microglia, the brains inner immune cells. These cells regulate inflammation in the brain and are involved in multiple brain disorders. Quantum dots are then transported to the microglias lysosomes, the cells garbage cans, for degradation.

But we also discovered that the behaviors of quantum dots vary slightly between cell cultures, brain slices and living animals. The simplified models may demonstrate how a part of the brain responds, but they are not a substitute for the entire organ.

For example, cell cultures contain brain cells but lack the connected cellular networks that tissues have. Brain slices have more structure than cell cultures, but they also lack the full organs blood-brain barrier its Great Wall that prevents foreign objects from entering.

Our results offer a warning: Nanomedicine research in the brain makes no sense without carefully considering the organs complexity.

That said, we think our findings can help researchers design quantum dots that are more suitable for use in living brains. For example, our research shows that PEG-coated quantum dots remain stable and relatively nontoxic in living brain tissue while having great imaging performance. We imagine they could be used to track real-time movements of viruses or cells in the brain.

In the future, along with MRI or CT scans, quantum dots may become vital imaging tools. They might also be used as traceable carriers that deliver drugs to specific cells. Ultimately, though, for quantum dots to realize their biomedical potential beyond research, scientists must address health and safety concerns.

Although theres a long way to go, my colleagues and I hope the future for quantum dots may be as bright and colorful as the artificial atoms themselves.

[ Like what youve read? Want more? Sign up for The Conversations daily newsletter. ]

Read the rest here:
Quantum dots that light up TVs could be used for brain research - The Conversation US

Prognostic Significance Of Platelet-To-Lymphocyte Ratio (PLR) And Mean | CMAR – Dove Medical Press

Xia-Bo Shen,1,2,* Yong Wang,2,* Ben-Jie Shan,2 Lin Lin,2 Li Hao,2 Yu Liu,1,2 Wei Wang,2 Yue-Yin Pan1,2

1Department of Medical Oncology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Peoples Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Yue-Yin PanDepartment of Medical Oncology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Peoples Republic of ChinaEmail yueyinpan1965@163.comWei WangDepartment of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Peoples Republic of ChinaEmail docweiwang@fsyy.ustc.edu.cn

Background: Small cell lung cancer (SCLC) is a special type of lung cancer and it is responsive to chemotherapy. Blood parameters have been proved to be associated with survival for many types of malignancies. This study aimed to investigate the prognostic significance of platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) for SCLC patients with etoposide-based first-line treatment.Methods: We retrospectively identified 138 patients diagnosed as SCLC who underwent etoposide-based first-line chemotherapy. The patients baseline clinical characteristics and blood parameters were collected. KaplanMeier analysis and Cox regression methods were used to determine the factors associated with progression-free survival (PFS).Results: The optimal cut-off value of diagnosis was depended on the ROC curve, the cut-off value of pretreatment PLR was 190 (sensitivity 39.0%, specificity 88.5%), and the cut-off value of pretreatment MPV was 10.0 (sensitivity 60.7%, specificity 61%). KaplanMeier analysis showed patients with high PLR levels in baseline had worse PFS than those with low PLR levels (P <0.001). Multivariate analysis revealed pretreatment MPV was an independent prognostic factor for PFS (HR: 0.815, 95% CI: 0.7110.933, P =0.003). Further research suggested continuous high PLR indicated a poor therapy outcome (P =0.002).Conclusion: Pretreatment MPV can be an independent predictor for first-line treatment outcome and a continuously high level of PLR suggested inferior PFS in etoposide-treated SCLC patients.

Keywords: small cell lung cancer, SCLC, first-line chemotherapy, mean platelet volume, MPV, platelet-to-lymphocyte ratio, PLR, prediction

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

The rest is here:
Prognostic Significance Of Platelet-To-Lymphocyte Ratio (PLR) And Mean | CMAR - Dove Medical Press

Global Regenerative Medicine Market: Analysis By Type (Cell Therapy, Tissue Engineered, Gene Therapy), By Application, By Region, By Country (2019…

arcognizance.com has added latest research report on Global Regenerative Medicine Market, this report helps to analyze top Key Players, regions, revenue, price, and also covers Industry sales channel, distributors, traders, dealers, Research Findings and Conclusion, appendix and data source.

As stated by the research report in August 2019, the Global Regenerative Medicine Market was valued at USD 22,814.45 million the year 2018. Driven by a number of differentiated fundamental factors including rise in the prevalence of chronic diseases and increase in medical research investments, the global market for regenerative medicine has been advancing at an augmented pace. The growth has been primarily driven by the search to find permanent cure of large number of incurable diseases such as various autoimmune and metabolic ailments, cancer, neurodegenerative disorders among others.

Over the recent years, regenerative medicine market has been witnessing considerable growth on the back of rising incidence of chronic diseases, rapidly growing medical research facilities, increasing investment by pharmaceutical manufacturers, and growing government initiatives. In addition, expanding product pipeline of companies and growing number of partnerships and collaborative agreements in this industry is anticipated to fuel the market growth in forecast period. However, high cost associated with the manufacturers and use of regenerative therapy has been hindering market growth.

Get Flat 15% Discount on Single User license and 20% Discount on Enterprise-wide User licenses Copy of this report, offer valid till 31th Dec,19

Request for Customization and Region Specific [emailprotected] https://www.arcognizance.com/enquiry-before-buying/573418

A comprehensive research report created through extensive primary research (inputs from industry experts, companies, stakeholders) and secondary research, the report aims to present the analysis of regenerative medicine market. The report analyses the Global Regenerative Medicine Market By Type (Cell Therapy, Gene Therapy, Tissue Engineered) and By Application (Orthopaedic and Dental, Cardiology, Wound Healing, Metabolism and Inflammation, Immunology & Oncology, Others). The global regenerative medicine market has been analyzed By Region (North America, Europe, Asia Pacific, and ROW) and By Country (U.S., Canada, U.K., Germany, France, Italy, China, Japan, India, Brazil) for the historical period of 2014-2018 and the forecast period of 2019-2024.

Scope of the Report

Global Regenerative Medicine Market (Actual Period: 2014-2018, Forecast Period: 2019-2024)

Global Regenerative Medicine Market- Size, Growth, Forecast

Analysis By Type: Cell Therapy, Gene Therapy, Tissue Engineered.

Analysis By Application: Orthopaedic & Dental, Cardiology, Wound Healing, Metabolism & Inflammation, Immunology & Oncology, Others

Download PDF Sample of Regenerative Medicine [emailprotected] https://www.arcognizance.com/enquiry-sample/573418

Regional Regenerative Medicine Market North America, Europe, Asia Pacific, ROW (Actual Period: 2014-2018, Forecast Period: 2019-2024)

Global Regenerative Medicine Market- Size, Growth, Forecast

Analysis By Type: Cell Therapy, Gene Therapy, Tissue Engineered.

Analysis By Application: Orthopaedic & Dental, Cardiology, Wound Healing, Metabolism & Inflammation, Immunology & Oncology, Others

Country Regenerative Medicine Market U.S., Canada, Germany, U.K, France, Italy, China, Japan, India, and Brazil (Actual Period: 2014-2018, Forecast Period: 2019-2024)

Global Regenerative Medicine Market- Size, Growth, Forecast

Analysis By Type: Cell Therapy, Gene Therapy, Tissue Engineered.

Analysis By Application: Orthopaedic & Dental, Cardiology, Wound Healing, Metabolism & Inflammation, Immunology & Oncology, Others

Other Report Highlights

Competitive Landscape:

Company Share Analysis

Collaborations, Partnerships and Alliances between Key Industry Players

Approved Product Analysis

Product Pipeline Analysis

Market Dynamics Drivers and Restraints.

Market Trends

Porter Five Forces Analysis.

SWOT Analysis.

Company Analysis Vericel, Gilead Sciences, Novartis, Spark Therapeutics, Orchard Therapeutics, MolMed, Celgene, Sanofi, Amgen, Shanghai Sunway Biotech.

Purchase this [emailprotected] https://www.arcognizance.com/purchase/573418

Customization of the Report

The report could be customized according to the clients specific research requirements. No additional cost will be required to pay for limited additional research.

Major Point of TOC:

Chapter One: Research Methodology

Chapter Two: Executive Summary

Chapter Three: Strategic Recommendations

Chapter Four: Regenerative Medicine Market: Product Outlook

Chapter Five: Global Regenerative Medicine Market : Growth and Forecast

Chapter Six: Global Regenerative Medicine Market : Segment Analysis

Chapter Seven: Global Regenerative Medicine Market : Regional Analysis

Chapter Eight: Global Regenerative Medicine Market: Competitive Landscape

Chapter Nine: Global Regenerative Medicine Market Dynamicscontinues

About Us:Analytical Research Cognizance is an initiation in this new era of analysis @ thought. We are on a mission to replace the conventional research programs and give way to the latest methods and information for the organizations. We have created this hub of analytical research papers where you can get an access to the latest and the best research papers coming out from some reliable and budding research houses.

Contact Us:Matt WilsonManager Global SalesAnalytical Research Cognizance+1 (646) 434-7969, +91 90967 44448[emailprotected]http://www.arcognizance.com/

Read the original post:
Global Regenerative Medicine Market: Analysis By Type (Cell Therapy, Tissue Engineered, Gene Therapy), By Application, By Region, By Country (2019...

NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through P | OTT – Dove Medical Press

Chengwu Gong,1,* Jiyuan Ai,1,* Yun Fan,2 Jun Gao,1 Weiwei Liu,1 Qian Feng,3 Wenjun Liao,1 Linquan Wu1

1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Peoples Republic of China; 2Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430000, Peoples Republic of China; 3Department of Emergency Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Linquan Wu; Wenjun LiaoDepartment of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang 330006, Peoples Republic of ChinaTel +86 791 86311529Fax +86 791 86262262Email wulqnc@163.com; liaowenjun120@163.com

Purpose: Studies show that high expression of non-SMC condensin I complex subunit G (NCAPG) is associated with many tumors. In this study, we explore the mechanism by which NCAPG promotes proliferation in hepatocellular carcinoma (HCC).Patients and methods: Liver cancer and paracancerous tissue specimens of 90 HCC patients were collected, and expression levels of NCAPG in these tissues and cell lines were evaluated by Western blotting and immunohistochemistry. HCC cells were transfected with siRNAs and plasmids, and pathway activators or inhibitors were added. The 5-ethynyl-2-deoxyuridine (EdU) proliferation assay was used to measure cell proliferation. Flow cytometry was used to evaluate cell apoptosis. Western blot assays were performed as a standard procedure to detect total protein expression. Treated HCC cells were subcutaneously injected into nude mice.Results: Analysis using the Oncomine database showed that NCAPG was upregulated in HCC and immunohistochemistry and Western blot assays showed it was upregulated in both HCC tissues and HCC cell lines. The overexpression of NCAPG could promote HCC cell proliferation and reduce HCC cell apoptosis. More importantly, RNA-sequencing analysis predicted that NCAPG plays a role in the HCC via PI3K-AKT signaling pathway. The PI3K/AKT/FOXO4 pathway was aberrantly activated, and the expressions of apoptosis-related protein were altered when NCAPG was overexpressed or silenced both in vitro and in vivo. LY294002, a PI3K inhibitor, could eliminate the NCAPG role of promoting HCC cell proliferation and reducing HCC cell apoptosis, while 740Y-P, a PI3K activator, contributed to the opposite effect.Conclusion: NCAPG functions as an oncogene in HCC and plays a role in promoting cell proliferation and antiapoptosis through activating the PI3K/AKT/FOXO4 pathway.

Keywords: NCAPG, hepatocellular carcinoma, PI3K/AKT, FOXO4, proliferation

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

View original post here:
NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through P | OTT - Dove Medical Press

Community Oncologist: A Key Player in CAR-T Cell Therapy – Cancer Therapy Advisor

Although administration of anti-CD19 chimeric antigen receptor (CAR)-T cell therapy takes place at authorized treatment centers, community oncologists still play an important role, particularly in the recognition of eligible patients and the management of adverse effects of the treatment.

Arecent piece in The Oncologist detailed this crucial element of CAR-Tadministration and highlighted key aspects of CAR-T cell indications andeligibility for community oncology providers.1

Tomaximize the chances of a patient receiving CAR-T cell therapy, communityoncologists should refer patients early and broadly, as the time of referralto CAR-T cell infusion can take 4 to 6 weeks.

Mostbroadly, patients with relapsed or refractory large B-cell lymphoma who havefailed on 2 or more prior therapies can be referred. Patients who have failedor relapsed after first-line immunochemotherapy may also be eligible.

Patientswho progress on first-line therapy should be referred directly to academiccenters whenever possible for management because high rates of relapse areobserved with second-line treatments, the authors wrote. Academic centers areequipped to facilitate a smooth and rapid transition to the next line oftherapy, especially CAR-T cell therapy, if patients are already receivingtreatment there, which may be particularly important for patients with rapidlyprogressing disease.

Aspart of this process, community oncologists should be aware of which centers intheir state offer CAR-T cell therapy.

Communityoncologists also play an important role in postinfusion care. Patients treatedwith CAR-T cell therapy are advised to carry a wallet card with them at alltimes that defines symptoms that could indicate a serious adverse event forwhich to seek medical attention. Any patient in response that does notexperience a serious adverse event after a 4- to 8-week stay returns home.

Thesepatients can experience prolonged hypogammaglobulinemia and B-cell aplasia, andsome patients may require supportive care with IVIG. Prolonged cytopenias canalso occur. Because the treatment causes immunosuppression, patients are atongoing risk for serious infections after discharge as well.

Coordinationand communication between the local oncologist and CAR-T cell treatment oncologistare important during the months after patients return home from their minimum4-week stay near the treatment center, the authors wrote. After this period,the authorized treatment center, in coordination with the local oncologist, mayhave patient follow-ups every 2 weeks until month 3, then decreasing infrequency to 6 months and 12 months after CAR T-cell infusion, then yearlyuntil 5 years after CAR T-cell infusion, the authors wrote.

Reference

See the original post here:
Community Oncologist: A Key Player in CAR-T Cell Therapy - Cancer Therapy Advisor

Cell therapy GammaDelta spins off Adaptive to direct body’s surveillance system – Endpoints News

If alpha beta T-cells the foundation of CAR-T cell therapy are killer cells, trained in the biologically ancient art of executing intruders, think of their gamma delta cousins as armed guards, capable of engaging an interloper but also of sounding an alarm to kick the rest of the bodys defenses into action.

The key role they play is to conduct immune surveillance, Natalie Mount told Endpoints News. And once they find an intruder they can stimulate a whole immune response as well as be cytotoxic [cell-killing].

Only discovered in 1985, these gamma delta T-cells () have already become a popular target in cancer immunotherapy. This morning, a top British biotech exploring potential applications founded a new company to help reach that goal as GammaDelta Therapeutics spun off Adaptate Biotherapeutics with Mount at its helm.

While GammaDelta will continue to focus on a CAR-T-like cell therapy approach, the new company will develop antibodies that guide the cells as they patrol a patient, Mount said.Both have the same aim: getting these cellular guards to notice and effectively strike cancers.

We are developing antibodies that are able to recognize the gamma delta cells and target those and modulate their activities, Mount said. Weve discovered a range of substrates and what we can do now is take that forward in non-clinical development.

Gamma delta cells have risen in popularity in oncology research largely because they show potential to bring cell therapys effectiveness in blood cancers to solid tumors, although they present other potential advantages, including broader targeting and faster response.

GammaDelta Therapeutics got in on the ground floor, opening its doors in 2016. Since then, new and bigger players have entered the game. Last week, Regeneron dropped $25 million as part of an $80 million funding round for Adicet Bio, another company looking to use antibodies to guide gamma delta T cells.

Just in the last 2 to 3 years theres been a real solid interest, Mount said.

The broad idea of targeting these cells for oncology is not new. Clinical trials have been conducted evaluating gamma delta T cell treatments on several cancers, including leukemia and sarcoma. They were safe but with highly limited efficacy, although some appeared for not-fully-understood reasons to actually fuel tumors.

But GammaDelta and Adaptate say they work on a different subset of cells than these earlier trials did, one called 2. 2 is found in the tissues, making it an intuitive weapon for attacking solid tumors.

The antibody concept behind Adaptate is an increasingly popular form of therapy. AbbVie, Eli Lilly, Regeneron, and Sanofi, among a long list of others, are developing a form of antibody therapy called bispecific. Theyre still in the early stage, but last year Bairds Brian Skorney argued that the class of drugs has huge potential.

Our bias is that bispecifics pose an existential risk to the cellular therapies, he wrote. If a regularly administered therapeutic can keep anti-tumor pressure on by consistently engaging and activating T-cells, we think the much more expensive CART would become an even harder sell than it already is.

The exhaustive CAR-T process is like a specialized masterclass in tumor-killing, with doctors withdrawing cells, equipping them with a specific antigen receptor to identify malignancies and re-injecting them. The antibody approach for Adaptate can be thought of more as directives from a command center guiding the surveilling immune cells.

GammaDelta will focus on a cell therapy process similar to CAR-T, while Adaptate focuses on antibodies. But Mount argued one of the big advantages for GammaDelta Therapeutics and gamma delta cells is that they can identify cancer cells based on patterns as opposed to the specific antigens that CAR-T (chimeric antigen receptor T-cells) therapies use, opening up the potential for a range of targets.

GammaDelta is much closer to the clinic than the Adaptate spinoff, although they have yet to reveal exactly when they will begin trials, and for what indications. Mount said they were at least 12 months from evaluating whether they were ready to enter the clinic.

Social image: Adaptive CEO Natalie Mount via GammaDelta

Read the original here:
Cell therapy GammaDelta spins off Adaptive to direct body's surveillance system - Endpoints News

Intellia Therapeutics Announces Presentations at the 2019 Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) – BioSpace

CAMBRIDGE, Mass., Oct. 16, 2019 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ: NTLA), a leading genome editing company focused on the development of curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, announced one oral presentation and four poster presentations were accepted for the 27th Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) taking place October 22-25, 2019, in Barcelona, Spain.

Intellias data includes important updates about the companys programs and platform development activities:

Oral Presentation:

In Vivo Gene Knockout Followed by Targeted Gene Insertion Results in Simultaneous Reduced Mutant Protein Levels and Durable Transgene Expression

Intellia will present data on its alpha-1 antitrypsin deficiency (AATD) program, which uses a modular hybrid delivery system combining lipid nanoparticle (LNP) encapsulated CRISPR/Cas9 with an adeno-associated virus (AAV) donor DNA template. Intellias gene knockout approach eliminates the production of the faulty PiZ variant of the protein, while targeted insertion of a wild-type gene copy facilitates production of a functional circulating protein. This builds on Intellias similar approach for targeted gene insertion of Factor 9, which achieved increased levels of circulating human Factor IX protein through two months in non-human primates and sustained through 12 months in mice.

Presenter: Anthony Forget, Ph.D.Abstract number: OR48Session 5b: New delivery systems and technologiesPresentation date/time: Friday, October 25, 2019, 11:30 a.m. 1:30 p.m. CETLocation: Room 113-115

Poster Presentations:

In Silico, Biochemical and Cell-Based Integrative Genomics Identifies Precise CRISPR/Cas9 Targets for Human Therapeutics

This poster presentation will highlight Intellias approach to assess off-target activity to identify highly specific CRISPR/Cas9 guides. Researchers demonstrated that potential off-target editing profiles discovered through empirical data from biochemical approaches were the most sensitive and accurate.

Presenter: Daniel OConnell, Ph.D.Poster ID Number: P655Date: Wednesday, October 23, 2019

Generation of a Library of WT1-Specific T Cell Receptors (TCR) for TCR Gene Edited T Cell Therapy of Acute Leukemia

This poster presentation focuses on Intellias ongoing research collaboration with IRCCS Ospedale San Raffaele to develop CRISPR/Cas9-edited T cell therapies to address intractable cancers, such as acute myeloid leukemia (AML). Researchers have successfully established a protocol enabling consistent and efficient tumor-specific TCR isolation and characterization from healthy donors. Based on these results, Intellia has selected multiple lead TCRs, which are undergoing development candidate evaluation.

Presenter: Erica Carnevale, Ph.D., Ospedale San RaffaelePoster ID Number: P111Date: Wednesday, October 23, 2019

Engineering of Highly Functional and Specific Transgenic T Cell Receptor (TCR) T Cells Using CRISPR-Mediated In-Locus Insertion Combined with Endogenous TCR Knockout

This poster presentation focuses on the companys T cell engineering technology, which is being applied in its Wilms Tumor 1 (WT1) lead ex vivo program. Intellia has identified an efficient CRISPR/Cas9-mediated process that inserts tumor-specific TCRs with high yield into the TRAC locus. Simultaneous knockout of the TRBC1 and TRBC2 loci substantially eliminates production of the endogenous T cell receptors.

Presenter: Birgit Schultes, Ph.D.Poster ID Number: P162Date: Thursday, October 24, 2019

CRISPR/Cas9-Mediated Gene Knockout to Address Primary Hyperoxaluria

This poster presentation will demonstrate the effects of independent CRISPR/Cas9-mediated knockout of each of two target genes involved in oxalate formation, lactate dehydrogenase A (LDHA) and hydroxyacid oxidase 1 (HAO1), to address primary hyperoxaluria type 1 (PH1).

Presenter: Sean Burns, M.D.Poster ID Number: P552Date: Thursday, October 24, 2019

About Intellia Therapeutics

Intellia Therapeuticsis a leading genome editing company focused on developing curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by permanently editing disease-associated genes in the human body with a single treatment course, and through improved cell therapies that can treat cancer and immunological diseases, or can replace patients diseased cells. The combination of deep scientific, technical and clinical development experience, along with its leading intellectual property portfolio, puts Intellia in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create a new class of therapeutic products. Learn more aboutIntellia Therapeuticsand CRISPR/Cas9 atintelliatx.comand follow us on Twitter @intelliatweets.

Forward-Looking Statements

This press release contains forward-looking statements ofIntellia Therapeutics, Inc.(Intellia or the Company) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellias beliefs and expectations regarding its planned submission of an IND application for NTLA-2001 in mid-2020; its plans to generate preclinical and other data necessary to nominate a first engineered cell therapy development candidate for its AML program by the end of 2019; its plans to advance and complete preclinical studies, including non-human primate studies for its ATTR program, AML program and otherin vivoandex vivoprograms; develop our proprietary LNP/AAV hybrid delivery system to advance our complex genome editing capabilities, such as gene insertion; its presentation of additional data at upcoming scientific conferences regarding CRISPR-mediated, targeted transgene insertion in the liver of NHPs, using F9 as a model gene, via the Companys proprietary LNP-AAV delivery technology, and other preclinical data by the end of 2019; the advancement and expansion of its CRISPR/Cas9 technology to develop human therapeutic products, as well as maintain and expand its related intellectual property portfolio; the ability to demonstrate its platforms modularity and replicate or apply results achieved in preclinical studies, including those in its ATTR and AML programs, in any future studies, including human clinical trials; its ability to develop otherin vivoorex vivocell therapeutics of all types, and those targeting WT1 in AML in particular, using CRISPR/Cas9 technology; the impact of its collaborations on its development programs, including but not limited to its collaboration withRegeneron Pharmaceuticals, Inc. or Ospedale San Raffaele; statements regarding the timing of regulatory filings regarding its development programs; and the ability to fund operations into the second half of 2021.

Any forward-looking statements in this press release are based on managements current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellias ability to protect and maintain our intellectual property position, including through our arbitration proceedings against Caribou; risks related to Intellias relationship with third parties, including our licensors; risks related to the ability of our licensors to protect and maintain their intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for our product candidates; the risk that any one or more of Intellias product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies will not be predictive of future results in connection with future studies; and the risk that Intellias collaborations withNovartisor Regeneron or its otherex vivocollaborations will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellias actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Intellias most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Intellias other filings with theSecurities and Exchange Commission. All information in this press release is as of the date of the release, andIntellia undertakes no duty to update this information unless required by law.

Intellia Contacts:

Media:Jennifer Mound SmoterSenior Vice PresidentExternal Affairs & Communications+1 857-706-1071jenn.smoter@intelliatx.com

Investors:Lina LiAssociate DirectorInvestor Relations+1 857-706-1612lina.li@intelliatx.com

See the article here:
Intellia Therapeutics Announces Presentations at the 2019 Annual Congress of the European Society of Gene and Cell Therapy (ESGCT) - BioSpace

Adaptate Biotherapeutics Formed To Develop T-cell Modulating Antibody-based Therapies – Technology Networks

Product News Oct 16, 2019

GammaDelta Therapeutics, a company focused on harnessing the unique properties of gamma delta (d) T-cells to develop transformational immunotherapies, has announced the formation of a spin-out company: Adaptate Biotherapeutics. While GammaDelta Therapeutics primary goal is to develop d T-cell based cell therapy products, the new spin-out will build on GammaDeltas knowledge to modulate d T-cell activity using therapeutic antibodies, with the potential to trigger an immune response against cancer.

d T-cells are a distinct T-cell sub-type that respond to molecular patterns of distress and have been shown to have tremendous potential in treating cancer and other immunological disorders. GammaDelta Therapeutics was formed in 2016 to harness these properties, and since then has gained knowledge of d T-cell biology developing a portfolio of investigational cell therapies poised to enter clinical development. In addition to gaining insight into cell growth and isolation, the companys scientists have also discovered a number of potential drug targets and antibodies that have potential to modulate the activity of d T-cells in situ.

Adaptate Biotherapeutics has been formed to further develop these targets and antibodies for therapeutic purposes and advance them into clinical studies. The two companies will continue sharing their insights into d T-cell biology as they work towards developing different therapeutic modalities.

Like what you just read? You can find similar content on the communities below.

To personalize the content you see on Technology Networks homepage, Log In or Subscribe for Free

See original here:
Adaptate Biotherapeutics Formed To Develop T-cell Modulating Antibody-based Therapies - Technology Networks