OMRF researcher named scientific director of OCASCR | Community … – Duncan Banner

OKLAHOMA CITY The Oklahoma Center for Adult Stem Cell Research (OCASCR) has named Oklahoma Medical Research Foundation scientist Lorin Olson, Ph.D., as its new scientific director.

OCASCR was founded in 2010 by the Oklahoma Tobacco Settlement Endowment Trust (TSET) to increase adult stem cell research in Oklahoma. Since then, OCASCR has funded research projects on diabetes, blindness, cancer and other illnesses at OMRF, Oklahoma State University, the University of Oklahoma and the OU Health Sciences Center.

Olson earned his undergraduate degree from Brigham Young University and his doctorate in biomedical science from the University of California, San Diego. Following postdoctoral training at the Fred Hutchinson Cancer Research Center in Seattle and the Mount Sinai School of Medicine in New York City, Olson launched his lab at OMRF in 2010. His work in the Cardiovascular Biology Research Program focuses on the intricate process of wound repair and the genes that control connective tissue development and disease.

Olson succeeds OMRFs recently appointed vice president of research, Courtney Griffin, Ph.D., as OCASCRs scientific director. In that role, he will oversee a semiannual review of grant applications from Oklahoma scientists to fund studies and equipment needed for specific research.

Olson plans to continue OCASCRs focus on adult stem cell research and regenerative medicine. Regenerative medicine is looking at how to use adult stem cells or their by-products to repair and restore diseased or damaged organs. Thats especially important in diseases related to smoking and obesity, both of which are focuses of TSET, he said.

TSET Executive Director Julie Bisbee said she is excited about the future of OCASCR and the role this research plays in TSETs overall goal.

TSET is proud to support OCASCR as their researchers develop new treatments for cancer and other tobacco-related diseases, said Bisbee. That work is key to TSETs mission and helps support scientific research and discoveries in Oklahoma. The work of this unique collaboration between academic and research institutions will be felt for generations to come.

Since OCASCRs founding, TSET has invested $31 million in Oklahoma scientists focused on adult stem cell research, with a return on that investment of more than $280 million in grants resulting from projects launched through the initiative.

See the rest here:
OMRF researcher named scientific director of OCASCR | Community ... - Duncan Banner

Blindness from Retinitis Pigmentosa reversed with MD Stem Cells treatment- benefit may last years – EIN News

RP patient improves from legal blindness to 20/20 vision following MD Stem Cell Treatment- wants to repeat

Steven Levy MD

WHAT'S NEW: The stem cell approach pioneered by MD Stem Cells has shown positive results helping patients suffering from a number of eye and neurologic diseases. In one of their initial scientific papers, MD Stem Cells showed that patients with Retinitis Pigmentosa or RP could benefit from the treatment provided in the Stem Cell Ophthalmology Treatment Study. That paper is titled Stem Cell Ophthalmology Treatment Study: bone marrow derived stem cells in the treatment of Retinitis Pigmentosa. We now see that these improvements can achieve normal acuity that results can last many years.

ACTUAL RESULTS: Results reported were all statistically significant- the gold standard in medicine for confirming results. 64.7% of patients showed improved binocular vision averaging 10.23 lines of Snellen acuity per eye over pre-treatment acuity; 35.3% of patients remaining stable over the follow up period. Improvements ranged from 1 to 27 lines of vision. Using the Logmar Scale visual acuity improvement ranged from 23% to 90% with an average of 40.9% visual acuity improvement over baseline vision. MD Stem Cells unique approach is the first and only treatment to actually improve and maintain vision in patients with RP.

WHAT IS THE TREATMENT: The Stem Cell Ophthalmology Treatment Study II ( SCOTS2) uses the patient's own stem cells for treatment. The patient is provide a short period of anesthesia and there is no pain. They take a small amount of the patients own bone marrow, isolate the stem cells, and provide 2 ocular injections followed by intravenous. .

OTHER EYE DISEASES THIS CAN HELP: MD Stem Cells has treated a number of eye diseases with benefit to vision. Retinal conditions such as dry AMD (macular degeneration), Retinitis Pigmentosa, Usher, Stargardt, Cone-Rod, Rod-Cone, Cone dystrophies, Bests dystrophy, different retinal problems including retinopathy, injury, inflammation, POHS ,choroiditis, some diabetic retinopathies and certain post Retinal Detachment vision loss. A number of optic nerve conditions have also responded including Glaucoma, LHON, Dominant Optic Atrophy, Optic neuropathies and many other optic nerve problems.

KEY POINTS: Retinitis Pigmentosa can now be treated with the SCOTS2 procedure with a high, statistically significant chance of improvement. Contact MD Stem Cells directly for a case review. MD Stem Cells has vast experience with eye disease and has published multiple medical and scientific papers. This is reassuring to patients and health care providers seeking treatment options. MD Stem Cells has the knowledge to carefully treat your retinal or optic nerve condition, if appropriate, leading to optimal results.

I WANT MORE INFORMATION: Receive information about participating in SCOTS2 by emailing Dr. Levy at stevenlevy@mdstemcells.com with your name, cell phone, email address and brief history of their disease. You may also use the contact us page on http://www.mdstemcells.com or call directly 203-423-9494. MD Stem Cells has no grant support and is not a pharmaceutical company; this is a patient sponsored studies and the patients pay for both treatment and travel.

Steven Levy MDMD Stem Cells+1 203-423-9494stevenlevy@mdstemcells.com

Go here to read the rest:
Blindness from Retinitis Pigmentosa reversed with MD Stem Cells treatment- benefit may last years - EIN News

Researchers develop method to identify, sort and observe function in neural stem cells – Medical Xpress

This article has been reviewed according to ScienceX's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

proofread

by Justin Jackson , Medical Xpress

Graphical abstract. Credit: Cell (2023). DOI: 10.1016/j.cell.2023.02.017

Researchers at Stanford University in California have devised a fluorescence-activated cell-sorting method for isolating distinct neural stem and progenitor cell types from human brain tissue. The markers used in the study are conserved across diverse brain regions. The technique should aid future research on neurodevelopment and accelerate the development of neuronal cell-transplantation-based therapeutic regimens to treat a host of neurological disorders.

In the research article, "Purification and characterization of human neural stem and progenitor cells," published in the journal Cell, the Stanford team describes the combination of cutting-edge methods they used to develop a reliable isolation and identification scheme to capture the stem cells of interest.

The human brain is home to about 171 billion individual cells, with just over half (~86 billion) being neuronal cells. Those 86 billion neuronal cells are a diverse group, with hundreds of dedicated types and functions, but all originate from three neuronal lineagesneurons, oligodendrocytes and astrocytes. The three lineages all start from a pool of neural stem and progenitor radial glia cells that undergo rapid development during the second trimester of prenatal gestation. Understanding these radial glia cells, how they differentiate into the three lineages and how the three lineages differentiate into the diverse range of neuronal cells would be of enormous benefit to medical research.

Fluorescence-activated cell sorting was used to separate brain tissue cell types by cell surface immunophenotype from a suspension of single cells. The cells were indexed (fluorescence recorded) and isolated from each other. The cells were then submitted to single-cell RNA sequencing to capture their individual transcriptomes. By combining the surface-marker profile with indexing and transcriptome, the researchers now had a profile of each cell type that could be used for later identification. Researchers also measured the expression of 352 additional surface markers not used in the initial separation scheme but which could be used to better differentiate cells in the future.

Index-sort data allowed for each sequenced cell to be mapped back to its original immunophenotype and the researchers discovered that RNA and cell-surface protein expression did not always correlate. Some similar looking cells might have different functions. The strategy resulted in functionally similar populations of sorted cells allowing for the isolation of specific neural stem and progenitor cell type functions to be analyzed.

Ten neural stem and progenitor cell types were identified, and the researchers looked to characterize the behavior of the cells by transplanting them directly into the brains of neonatal immunodeficient mice. After six months, the cells had migrated and engrafted extensively throughout the brain and differentiated to give rise to all three major neural lineages. By observing how and where individual cell types propagated, the researchers could make some initial inferences about site-appropriate activities. Though the experiment was meant simply as a method viability test, researchers did identify and functionally characterize a distinct bipotent glial progenitor cell that had not been previously described.

The Stanford team's successful proof of concept (with a discovery) that distinct cell types from the developing brain can be isolated based on surface markers could be readily adapted by other research scientists, as it operates on relatively standard research equipment. If the method used can be replicated for other stem cell types, there could be a surge in our understanding of specific functions, mechanisms and hierarchical roles that cells play in the brain or in other organs.

More information: Daniel Dan Liu et al, Purification and characterization of human neural stem and progenitor cells, Cell (2023). DOI: 10.1016/j.cell.2023.02.017

Journal information: Cell

2023 Science X Network

Original post:
Researchers develop method to identify, sort and observe function in neural stem cells - Medical Xpress

Using stem cells to prevent brain damage in very preterm babies – Monash University

You are here:

21 March 2023

Australian researchers have conducted the first attempts to collect umbilical cord blood cells from very preterm babies, with a view to using them to reduce their increased risk of brain injury and disability.

The trial was conducted at Monash Childrens Hospital Melbourne, Australia, led by Dr Lindsay Zhou, under the supervision of Professor Atul Malhotra, Co-Director of the Newborn Cell Therapies Group from the Department of Paediatrics at Monash University and published recently in the journal Cytotherapy.

Cord blood is the blood left in the umbilical cord and placenta of newborn babies after birth. It is rich in stem cells which can be used to help protect, repair and grow cells in the body, and according to Dr Zhou these cells have shown strong promise as a treatment for neonatal brain injury in pre-clinical models and early-phase clinical trials. While it has been tested in infants born at term, these life-giving cells have not been tested in preterm babies, who arguably have the greatest need for new treatments because their risk of brain injury and disability later in life is so much greater, he said.

The researchers, who are also from The Ritchie Centre at the Hudson Institute of Medical Research, took cord blood from 38 infants born before 28 weeks gestation. Babies born extremely preterm (<28 weeks) have a high chance of long-term developmental issues, including cerebral palsy, and learning and behavioural issues.

Of the babies included in the trial, 21 were male and 17 female. Twenty-four (63.1%) were delivered via caesarean section, and 11 (28.9%) were a multiple birth. The average age of the baby in this study was 26 weeks gestation, and the average birth weight was 761.5 grams.

The researchers were able to collect an average of 19 ml/kg of cord blood from these preterm babies, which is similar to term babies by body weight. The procedure was successful in 72% of cases. According to Professor Malhotra, these findings are important because we have shown we can collect these cells in extremely small babies, and can now use them in the CORD-SAFE study currently underway at the Monash Childrens Hospital.

The CORD SAFE study is investigating the feasibility and safety of administering autologous (their own) cord blood cells to these extreme premature infants. The study is nearing completion phase, with results likely by the end of the year.

Read the full paper in Cytotherapy journal titled: Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants.

DOI: 10.1016/j.jcyt.2023.01.001

About Monash University

Monash University is Australias largest university with more than 80,000 students. In the 60 years since its foundation, it has developed a reputation for world-leading high-impact research, quality teaching, and inspiring innovation.

With four campuses in Australia and a presence in Malaysia, China, India, Indonesia and Italy, it is one of the most internationalised Australian universities.

As a leading international medical research university with the largest medical faculty in Australia and integration with leading Australian teaching hospitals, we consistently rank in the top 50 universities worldwide for clinical, pre-clinical and health sciences.

For more news, visitMedicine, Nursing and Health Sciences orMonash University.

MEDIA ENQUIRIES

E:media@monash.edu

Originally posted here:
Using stem cells to prevent brain damage in very preterm babies - Monash University

Cell Therapy Prevents Risk Of Heart Attack or Stroke: Study – Forbes

All organs in the body rely on the blood and oxygen circulated by the heart. If the muscles of the heart weaken or stiffen too much, the heartalthough still beatingcan no longer pump enough to sustain other organs. This progressive condition called heart failure presently affects more than 6 million adults in the United States. Current treatments can delay but not permanently alter the course of the disease, leaving many patients with poor prognoses. A recent study published in the Journal of the American College of Cardiology searches for a permanent solution to repair the heart via stem cell therapy.

What are Mesenchymal Stem Cells?

Mesenchymal precursor cells (MPCs) refer to a small population of adult stem cells found in the bone marrow and select tissues. While embryonic stem cells can develop into any cell type in the body, mesenchymal stem cells develop into a defined variety of specialized cells. As Figure 1 illustrates, differentiation of these cells can create connective tissue cells, cartilage cells, white fat cells, bone cells and muscle cells. The ability to regenerate muscle cells is of notable interest in discussions around healing damaged hearts.

Mesenchymal precursor cells demonstrate other unique abilities. Preclinical studies suggest that these precursor cells may reduce inflammation driven by macrophages, immune cells involved in the bodys healing processes, and chemicals called cytokines. These stem cells also release proteins which promote the growth of new blood vessels and reverse the narrowing of arteries. These two characteristics may address critical mechanisms which contribute to heart failure: acute and chronic inflammation alongside restricted blood flow to the hearts tissues.

Clinical Trial Design

For their study, Perin et al. assessed the efficacy of mesenchymal precursor cell therapy on over 500 patients with moderate to severe heart failure. To do this, they first crafted their stem cell product. The researchers derived the stem cells from the bone marrow of three healthy adult donors. They then isolated and proliferated the stem cells before preserving them in liquid nitrogen.

Of all the hearts chambers, the team focused on the left ventricle. Figure 2 highlights the structure. This section of the heart provides the most pumping power and often falters first for people with heart failure. Left ventricular performance is therefore an important marker of the hearts condition.

Half of the study population received at least one dose of the cell therapy injection (see Figure 3) into the left ventricle. In contrast, the other halfthe control groupunderwent a procedure to remove a catheter from the left ventricle. The researchers then conducted site follow-ups 10 days after and on months 1, 3, 6 and 12. After month 12, the patients returned to the site every six months. The team followed the patients for around 30 months on average.

Study Endpoints and Measurements

The study contained two main objectives to understand the potential benefits of the intervention. The primary endpoint measured whether the therapy prolonged the time to a patients next nonfatal hospitalization or urgent care visit; it was considered a terminal event if a patients left ventricle failed to provide the majority or any of the hearts output. The secondary measurement recorded both the primary endpoint and the time to death.

Guided by a previous study, the team monitored left ventricular function and markers of inflammation for additional analysis. Left ventricular performance plays a major role in determining heart failure, while high baseline levels of high-sensitivity C-reactive protein (hsCRP)a marker of inflammationin patient plasma is associated with adverse cardiac events.

Mixed Results

The clinical trial yielded mixed results. The team found no significant difference between the treatment groups for the studys primary and secondary endpoints, suggesting that the therapy did not succeed. However, the therapy produced major findings related to heart function which hold great promise for future research.

Inflammation, Heart Attack and Non Fatal Stroke

The team noticed that adverse heart events could be stratified by inflammation. A single stem cell injection resulted in a 67% reduction in heart attack and a 56% reduction in stroke compared to controls. Figure 4 illustrates the clear difference in risk. Interestingly, the supposed benefit increased if the patient displayed higher levels of inflammation (see Figure 5).

Additionally, the therapy led to a modest reduction38% specificallyin three point major adverse cardiovascular events. This is categorized by a cardiovascular death, nonfatal heart attack or nonfatal stroke. Patients with more detectable inflammation saw a larger effect here, as well.

Inflammation and the Left Ventricle

The team used echocardiographic imaging to glean information about the left ventricle. They recorded three measurements in particular: left ventricular ejection fraction (LVEF), or how much blood the left ventricle pumps out during each heartbeat; left ventricular end-systolic volume (LVESV), or how blood remains in the chamber after a heartbeat; and left ventricular end diastolic volume (LVEDV), how much blood is in the chamber before a heart beat.

The patients who received the cell therapy experienced a small but statistically significant improvement in their hearts ability to pump over the course of a year. This is mostly attributed to the effect experienced by patients with higher levels of inflammation. In comparison, the therapy did not influence the left ventricular diastolic volume when compared to controls.

Possible Mechanisms

The clinical hope for cell therapy is to harness the self-renewing and tissue regenerating capabilities of stem cells to heal and repair the body. The mesenchymal stem cells injection in this study did not meet this goal; the therapy failed to reduce time to nonfatal hospitalization and all cause death for patients with heart failure. However, an interesting discovery did emerge regarding inflammation.

The stem cell therapy created by Perin et al. yielded larger perceived benefits for patients with higher detectable levels of inflammation. Heart attack, stroke and left ventricular function appeared to improve for patients with evidence of systemic inflammation. How could this difference be explained?

Background research suggests that targeting inflammation could reduce negative heart events. Animal studies of heart failure demonstrated how mesenchymal precursor cells could rebuild and generate new blood vessels; they, too, could reverse the narrowing of arteries throughout the heart and body in the presence of systemic inflammation. The authors posit, then, that their cell therapy may alter inflammatory environments in the heart and promote blood flow through the formation of new blood vessels.

The cytokines found around the heart may activate the mesenchymal cells, causing the stem cells to subsequently release proteins which suppress inflammation and encourage blood vessel formation. The anti-inflammatory effects likely reduce nonfatal heart attack, stroke and death for patients with high inflammation. On the other hand, the new blood vessels likely improve the function of the left ventricle, as noted in the study.

As the stem cells appear to target local and systemic inflammatory changes seen in heart failure and atherosclerosis (plaque-filled arteries), Perin et al. turn to inflammation as a possible therapeutic target for heart failure. The therapy, when used in conjunction with existing heart failure treatments, may provide additional clinical benefit to patients with increased inflammation.

Future Implications

This clinical trial marks an important step in the journey to use cell therapy to reverse heart failure. Although the therapy did not prevent hospitalization as initially hoped, the researchers found that a single stem cell injection reduced the risk of heart attack or stroke by more than 50% for people with heart failure. Stem cell therapy may be a complementary addition to heart failure treatment regimes in the future, but further research is needed to ascertain its promise.

I am a scientist, businessman, author, and philanthropist. For nearly two decades, I was a professor at Harvard Medical School and Harvard School of Public Health where I founded two academic research departments, the Division of Biochemical Pharmacology and the Division of Human Retrovirology. I am perhaps most well known for my work on cancer, HIV/AIDS, genomics and, today, on COVID-19. My autobiography, My Lifelong Fight Against Disease, publishes this October. I am chair and president of ACCESS Health International, a nonprofit organization I founded that fosters innovative solutions to the greatest health challenges of our day. Each of my articles at Forbes.com will focus on a specific healthcare challenge and offer best practices and innovative solutions to overcome those challenges for the benefit of all.

Link:
Cell Therapy Prevents Risk Of Heart Attack or Stroke: Study - Forbes

Rise in Prostate Cancer Cases Contributes to Challenges in Care – Targeted Oncology

Murugesan Manoharan, MD, FRACS

Troubling news about prostate cancer emerged from the American Cancer Society (ACS) in January. In its Cancer Statistics 2023 study1, published in the journal CA: A Cancer Journal for Clinicians, ACS scientists announced:

These findings are due in part to the US Preventive Services Task Forces 2012 recommendation to cease PSA screening in all men. Since then, early diagnosis and treatment of prostate cancer has dropped, while advanced prostate cancer cases have begun a steady rise.

I have observed several factors in play at Miami Cancer Institute as we respond to the challenge of prostate cancer.

Cost of PSA Screening

I concur with the ACS recommendation that men of all ages should have an opportunity to make an informed decision about whether prostate cancer screening is right for them. Balanced and unbiased counsel from the physician is vital. However, the cost of testing may be a barrier for some patients, as many insurance plans do not cover it. I have observed that wealthier patients in urban areas are more likely to have access to timely screening, while lower-income and minority individuals do not. The latter group includes many of my patients in the Haitian American community, who have a significant incidence of aggressive prostate cancer.

Plentiful Treatment Options

The array of prostate cancer treatments includes robotic surgery, external beam radiation including proton beam therapy, brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), laser ablation, hormone and other drug therapy, chemotherapy, immunotherapy, and more. Direct-to-consumer marketing touting these various treatments can confuse and overwhelm patients. Again, careful consultation with an unbiased urologic oncologist is critical.

Image Credit Sheitipaves [stock.adobe.com

FDA Reviews

While the US is quite advanced in prostate cancer treatment, The FDAs ultra-cautious approach to approvals results in a lag in new-technology adoption.

For example, prostate specific membrane antigen (PSMA PET Imaging, which can accurately detect the spread of prostate cancer spread using a radioactive tracer, has been in use internationally since around 2014, but the FDA delayed its broad national approval of this technology until 2021.

High Intensity Focused Ultrasound (HIFU) therapy was studied as early as the 1940s and researchers focused on HIFU for the prostate in the 1990s. The treatment was approved in more than 20 countries, including Canada and Australia, before finally receiving FDA approval in 2015.

Last, the NanoKnife system, which employs low-energy, direct-current electrical pulses to destroy cancerous cells,was first made commercially available in 2009 but the FDA approved a pilot study only in 2019.

These technologies were widely used in cancer centers around the US prior to full FDA approval but since they werent covered by insurance, they were out of reach for many patients who could have benefited.

Promoting Good Quality-of-Life

Death isnt the only outcome of a prostate cancer diagnosis. The statistics dont account for the pain, suffering, and inconvenience patients may endure while undergoing treatment. My team and I focus on helping patients maintain a good quality of life while we work towards a cure. Our patients express several priorities as they prepare for prostate cancer treatment:

A quick recovery: patients want to get back to work and everyday living. Technological advances such as minimally invasive surgery (sometimes with a single small incision) help make this possible. Many patients go home 24 hours after surgery. Once their pain can be managed without narcotics, they can usually resume driving and other daily tasks.

Reliable urinary function: patients frequently express concerns about incontinence. Twenty years ago, some 10 percent of patients were left incontinent by prostate surgery. Because we are now able to better protect the nerve bundles and urinary sphincter during surgery, 98 percent of patients do not need pads one year after surgery.

A healthy sex life: while measuring sexual potency is subjective, I advise patients that if they are potent before surgery, theres a 75 to 90 percent chance they will remain potent after nerve-sparing surgery.

Managing treatment: traditional radiation treatments can require up to 6 weeks of daily hospital visits, a burdensome task for patients who are trying to hold down a job. Hyperfractionated radiotherapy uses higher doses of radiation spread over fewer days, allowing patients to keep a regular work schedule. Ablation therapy requires even less of a time commitment.

Novel treatment strategies

Novel treatment like theranostics are on the rise. Theranostics combines therapeutic, radioactive pharmaceutical particles with diagnostic imaging to examine cancerous cells. In prostate cancer patients, a PSMA PET scan is done to evaluate for metastatic disease. PSMA, or prostate-specific membrane antigen, is expressed by virtually all prostate cancers and its presence locates the cancerous cells accurately. When these cells and receptors are located, a theranostic medicine such as Lutetium-177 in combination with PSMA is administered, which binds to and kills the cancerous cells. Its use is currently limited to prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer.

Training

As prostate cancer diagnoses continue to rise, todays physicians have a duty to prepare the next generation in the fight. Miami Cancer Institute, in concert with Florida International Universitys Herbert Wertheim College of Medicine, offers a two-year Urologic Oncology fellowship covering all treatment modalities.

We also work with Year 3 and 4 medical students who havent yet chosen a specialty. Its my job to introduce them to the challenges of our super-specialty and pique their interest in pursuing urologic oncological surgery.

Lastly, we support working physicians who desire to continue their education in the specialty. My colleagues and I offer surgical observation opportunities for local physicians as well as participate in international training programs.

The advent of teleconferencing has created exciting new training opportunities. We offer bimonthly telemedicine webinars through Baptist Urological Academy to an international audience. Many participating physicians and fellows become recognized urologic oncologists in their own countries.

Managing prostate cancer starts with screening and early diagnosis but extends into the effective management of prostate cancer. It requires constructive participation of all involved in the prostate cancer management including the government, health institutions, physicians, health care staff and most importantly, the patients.

REFERENCES

1, Siegel RL,Miller KD,Wagle, NS,and Jemal A, A.Cancer statistics, 2023.CA Cancer J Clin2023;73(1):17-48. doi:10.3322/caac.21763

Read the rest here:
Rise in Prostate Cancer Cases Contributes to Challenges in Care - Targeted Oncology

FDA Approval Makes Pharming Drug First for Rare Inherited … – MedCity News

A rare immunodeficiency discovered just 10 years ago now has its first treatment. The FDA has approved a Pharming Group drug developed to treat activated phosphoinositide 3-kinase delta syndrome, or APDS, a disease that leads to low levels of white blood cells that fight pathogens and prevent infection.

The FDA said Friday that its approval of the drug, lenolisib, covers adults as well as children 12 and older who have APDS. Leiden, Netherlands-based Pharming will market its new twice-daily pill under the name Joenji.

APDS is caused by mutations to genes that encode PI3KD, a protein key for normal development and function of white blood cells. The disease particularly affects B and T cells, resulting in cells that improperly mature and malfunction. The disorder makes patients more susceptible to recurrent infections in the sinuses, ears, and respiratory tract. It may also lead to enlarged lymph nodes, tonsils, spleen, and other organs, which can obstruct the airways and gastrointestinal tract. Furthermore, this protein deficiency also makes patients more prone to developing blood cancers.

The overlapping symptoms of primary immunodeficiencies lead to APDS frequently being misdiagnosed. The disease was first characterized in 2013 and can now be diagnosed with genetic testing. According to Pharming, APDS affects an estimated 1 million to 2 million people worldwide. Treatment has consisted mainly of symptom management: prophylactic antibiotics, immunoglobulin replacement, and immunosuppression. If lymphomas develop, chemotherapy and stem cell transplants are treatment options, but these treatments introduce new complication risks.

Joenji is a small molecule designed to block the PI3K-delta protein, an approach intended to inhibit signaling pathways that lead to dysregulation of B cells and T cells. FDA approval of the drug is based on a placebo-controlled Phase 2/3 study that enrolled 31 adults and children 12 and older with a mutation PI3K-delta mutation. The FDA said results showed that by day 85 of the study, patients in the Joenja group showed a reduction in the size of their lymph nodes and normalization of their levels immune cells, as measured by calculating the percentage of nave B cells out of total B cells, indicating improvement.

Pharming already has one FDA-approved product, the hereditary angioedema drug Ruconest. In 2021, that drug accounted for 198.8 million in revenue, down 9% from the prior year. Pharming licensed Joenji from Novartis in 2019, paying $20 million up front. The two companies partnered on Phase 2/3 testing. An additional $200 million is tied to the achievement of regulatory and sales milestones. Novartis is also entitled to receive royalties from Pharmings sales of the new drug.

FDA approval of Joenja comes with a priority review voucher (PRV) that entitles Pharming to receive speedy review of a future rare disease drug. Pharming said that according to the terms of the companys license agreement with Novartis, the pharmaceutical giant has the right to purchase this voucher for a small minority share of the value of the PRV.

Pharming has scheduled a Monday, 8 a.m. Eastern time conference call to discuss Joenjas approval.

Image by Flickr user NIAID via a Creative Commons license

Read more from the original source:
FDA Approval Makes Pharming Drug First for Rare Inherited ... - MedCity News

Delivery Matters: In Early Studies, DPX Technology Allows Vaccines … – AJMC.com Managed Markets Network

As cancer treatments have evolved, scientists have worked to improve 2 things: making the responses to therapy last longer, and limiting how much collateral damage the therapy does as it attacks the tumor. The arrival of immunotherapy has been monumental: across many types of cancers, response rates to immunotherapy are higher, deeper, and more durable than with chemotherapy.1 When responses occur, adverse events in immunotherapy are different but manageable, and quality of life is improved.

Still, not every patient benefits. Not everyone responds, and despite the advances of the last decade, some cancers have high rates of recurrence; ovarian cancer, for example, has a rate of 85%.2 For all the wonders of chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL), about 40% of patients relapse.3 Thus, the quest continues for treatments that last longer with fewer adverse events (AEs); in the United States, this may also allow the patient to keep a job that provides health coverage.

It's these highly refractory patients that the biotech IMV is enrolling in trials, so it can examine its novel delivery platform for immunotherapy, one designed to teach the bodys immune systemincluding the innate immune systemto deliver a sustained response against cancer. Based on promising results, including the SPiReL study in DLBCL,4-5 IMV has moved into phase 2b trials in both DLBCL and ovarian cancer with its lead therapeutic candidate, maveropepimut-S (MVP-S), which is a cancer vaccine composed of survivin epitopes that uses the companys proprietary delivery system, called DPX.

The VITALIZE Phase 2b trial (NCT04920617) is a randomized, parallel group 2-stage study that will evaluate MVP-S with pembrolizumab (Keytruda) in patients who have received at least 2 lines of systemic therapy and are ineligible for or have failed autologous stem cell transplant (ASCT) or CAR T therapy. Positive preliminary data from VITALIZE were shared February 13, 2023, at the IO 360 meeting in New York, New York.6 Data shared showed:

A phase 2b, single-arm study called AVALON (NCT05243524) involves MVP-S with intermittent low-dose cyclophosphamide in patients with platinum-resistant ovarian cancer.7 The MVP-S agent with pembrolizumab combination is also being studied in bladder cancer.8

Vaccines That Persist in Fighting Cancer

In an interview with Evidence-Based Oncology, (EBO) prior to the IO 360 presentation, Jeremy Graff, PhD, explained the science behind the DPX platform. Most people are familiar with prophylactic vaccinessuch as those that prevent polio, measles, or COVID-19which he said are used to prevent a disease from taking root. Therapeutic vaccines, Graff said, must accomplish a different task. Not only must they create a response that works immediately against the disease, but they must also generate a response that is persistent, meaning it keeps working against the disease despite the microenvironment that the cancer or chronic illness has setup to insulate against an attack.

With a prophylactic vaccine, When we educate our response to poliovirus, there's nothing that pushes back against that response, Graff explained. By contrast, when we educate a response to a cancer protein, the cancer itself is pushing back against that response all the time.

Cancer vaccines have failed in the past, he said, because they have not generated this persistent response. Prior efforts have tried to deploy a prophylactic strategy, with the hope that would become therapeutically useful. Instead, Graff said, the immune response is temporarily ignited but ultimately shuts down, in many cases by the cancer itself.

DPX takes an entirely different approach by packaging its vaccine, or other cancer-fighting cargo, in a way that ignites the innate immune system, so that it digests the key antigens that we want the immune system to pay attention to, he said. Instead of flooding the patient with poorly targeted chemotherapy or more precise immunotherapy, Graff explained, the DPX platform works to hand deliver antigens with the right signals to the T cells and B cells of the adaptive immune system, so they are trained in waves to fight cancer.

Carrying the Cargo in Oil

Our formulation is very different, Graff said. We resuspend our immune-educating cargo, whether theyre antigens in the form of proteins, or peptides, or RNAs, in an oil. And then we inject that oil-based solution into the subcutaneous space.

The solution stays put until the antigen-presenting cells of the innate immune system arrive to carry the injection to the lymph nodes, where they can work against cancer. Prior systems just let vaccines fall part in tissue, Graff explained.

It takes time to carry the injection to the lymph nodes, and with the DPX system investigators allow 60 days for the vaccine to be carried through the immune system; then another injection starts the process again. EBO asked Graff: does each patients innate immune system deliver the vaccine on the bodys own timetablecreating, essentially, a new type of personalized medicine?

You can kind of think of it that way, Graff responded. When the antigen-presenting cells pick up on the vaccine, they do so along with whatever bacteria, fungi, or viruses an individual already brings to the system. Whatever the immune system looks like, the antigens still train the T and B cells.

Can the DPX technology, with its oil-based solution, work with other cancer-fighting agents besides what is currently under study? Graff says yes. We think we can take all different types of cargo, he said. The lead product is licensed from Merck KGaA (Germany); it had been tested with a standard emulsion, but no clinical benefit was seen. Used with DPX, Graff said, We now see a much more robust immune responseits much more persistent. It leads to clinical benefit and has done so in multiple cancer types.

Could this mean that molecules that showed promise in mouse models but didnt pan out in early human trials could see new life with DPX technology?

Absolutely, Graff says enthusiastically. We can package whole viruses, we can package large proteins, multiple proteins, antigens, RNAswe can do all sorts of stuff with our formulation, he said.

We would say in a short way, delivery matters, Graff said. If you don't deliver antigens to the immune system correctly, you can't expect the immune system to react correctly.

Will the Markets Respond?

Despite the previous findings and well-received preliminary VITALIZE data presented at IO 360, IMV finds itself in a quandary. In a March 16, 2023, conference call to discuss annual fiscal year-end financials, CEO Andrew Hall was at a loss to explain the recent sell-off of IMV shares. That fact that we have seen the same number of complete responses in the first handful of patients as we had seen for the whole SPiReL trial, and those complete responses have been confirmed by at least 2 scansone at 70 and one at 140 daysis, to say the least, encouraging, he said during the call.9

The current financial landscape for small biotechs is challenging, Hall said. It's for this reason, we've engaged our long-time partner, Stonegate, to help us explore strategic options in this difficult market, he said.

Hall also wanted investors to understand just who the patients are that IMV is reaching. I want to highlight one of those complete responses in VITALIZE that was presented at the recent IO 360 meeting in New York. This patient is young man, 24 years old. His disease had progressed through standard rituximab-based therapy, then stem cell transplant, and, more recently, through CAR T therapy.

He was running out of options, Hall continued. He enrolled in the VITALIZE trial last fall. On his first scan 70 days later, his disease was gone. On his second scan, he is a complete confirmed responder. For the first time since diagnosis, this patient is back at the gym and doing things a 24-year-old should be doing.

Graff explained why 2 patients could not stay on study. The trial criteria call for patients to have a life expectancy of at least 90 days; some patients simply are not making it through the screening phase.

In its March 16, 2023, statement, IMV said it will complete stage 1 enrollment in VITALIZE (30 patients) during the second quarter of 2023; it will complete stage 1 enrollment of AVALON in the third quarter of 2023 (approximately 40 patients), and will present preliminary phase 1 data involving MVP-S and the DPX platform in non-muscle invasive bladder cancer in third quarter of 2023.10

References

1. Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17(8):807-821. doi:10.1038/s41423-020-0488-6

2. Blevins Primeau AS. Cancer recurrence statistics. Cancer Ther Adv. November 30, 2018. Accessed March 21, 2018. http://bit.ly/3FGfwMj

3. Larson RC, Maus MV. Recent advances and discoveries in the mechanism and functions of CAR T cells. Nat Rev Cancer. 2021;21(3): 145161. doi:10.1038/s41568-020-00323-z

4. Berinstein NL, Bence-Buckler I, Forward NA, et al. Clinical effectiveness of combination immunotherapy DPX-Survivac, low dose cyclophosphamide, and pembrolizumab in recurrent/refractory DLBCL: the SPiReL study. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 4-8, 2020; virtual. Abstract 2114. http://bit.ly/3lwM9Fb

5. IMVs survivin-targeted T cell therapy shows durable clinical benefits in phase 2 study in patients with hard-to-treat advanced recurrent ovarian cancer. News release. IMV Inc. December 3, 2020. Accessed March 21, 2023.https://bwnews.pr/3lDxzWu

6. IMV Inc. presents positive initial results from the MVP-2 phase 2b VITALIZE trial. News release. IMV Inc. February 13, 2023. Accessed March 21, 2023. http://bit.ly/3FFCW4e

7. IMV Inc. announces update and planned 2023 milestones to advance clinical development of its lead therapeutic, MVP-S. News release. January 8, 2023. http://bit.ly/3JY8ftN

8. Our clinical pipeline. IMV Inc. Accessed March 21, 2023. https://www.imv-inc.com/pipeline

9. Fourth quarter and fiscal year 2022 results webcast. IMV Inc. website March 16, 2023. Accessed March 17, 2023. http://bit.ly/3JrK7hC

10. IMV Inc. announces strategic update as well as fourth quarter and full year 2022 and financial and operational results. News release. IMV Inc. March 16, 2023. Accessed March 17, 2023. http://bit.ly/3ltNSv3

See original here:
Delivery Matters: In Early Studies, DPX Technology Allows Vaccines ... - AJMC.com Managed Markets Network

When to Use Second-Line CAR T-cell Therapy for Relapsed … – Targeted Oncology

Gilles Salles, MD

Chief of Lymphoma Service

Steven A. Greenberg Chair

Memorial Sloan Kettering Cancer Center

New York, NY

Targeted OncologyTM: How do the National Comprehensive Cancer Network (NCCN) guidelines recommend treating patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) based on the outcomes of first-line therapy?

SALLES: [Looking at] the NCCN guidelines, for patients with the intention to proceed to autologous stem cell transplant (ASCT), second-line therapy is divided by complete responders with ASCT, partial responders [who] usually go to CAR [chimeric antigen receptor] T-cell therapy, and those with progressive disease who will go to salvage therapy or CAR T-cell therapy.1 Patients with relapsed disease within 12 months, or primary refractory disease, should envision CAR T-cell therapy and the nontransplant candidates will go to a couple of suggested regimens.

If we go back to those patients with the intention to treat with CAR T-cell therapy, we have to think of patients a little differently from [the way one is] used to thinking. Were used to seeing patients [in terms of being] eligible or ineligible for ASCT. [Now,] for these [patients relapse] early, [we have to ask if they] are eligible for CAR T-cell therapy and decide who is more [optimal] for CAR T-cell therapy. Thats probably a good discussion [to have]. In this case, we have both axicabtagene ciloleucel [axi-cel; Yescarta] and lisocabtagene maraleucel [liso-cel; Breyanzi] available for patients.

At what point can CAR T-cell therapy be used for patients with relapsed/refractory DLBCL?

Regarding their [FDA] approvals, axi-cel was approved for patients who are refractory to first-line therapy or relapse within 12 months of first-line chemoimmunotherapy.2 The way we all interpret that is 12 months from the end [of first-line therapy], though initially some of the trials [did otherwise]. Liso-cel has a slightly different label: refractory disease or first-line relapse within 12 months of first-line therapy, then there is an addendum which is based on the study: refractory disease to first-line chemoimmunotherapy or relapsed after first-line chemoimmunotherapy and not eligible for ASCT.3

For axi-cel, the ZUMA-7 trial [NCT03391466] was taking patients from the time of relapse, [performing] apheresis on the patient, bridging them with steroids but not with chemotherapy, which may make [a difference].

What were the efficacy outcomes of the phase 3 trials investigating second-line CAR T-cell therapy?

[There were] 3 trials [of CAR T-cell therapy for DLBCL], ZUMA-7, BELINDA [NCT03570892], and TRANSFORM [NCT03575351].4-6 Patients were in the range of 55 to 60 years of age [on these trials]. They had the same criteria of eligibility; all these patients [relapsed after] less than 12 months. In ZUMA-7, the only bridging therapy was steroids whereas BELINDA, the one with tisagenlecleucel [tisa-cel; Kymriah] and TRANSFORM with liso-cel were offering the possibility of 2 or 3 cycles of chemotherapy as bridging therapy.

Two-thirds to three-quarter of patients were refractory, [and approximately] 25% were relapsed [across these studies]. The median follow-up was quite different; [approximately] 2 years for ZUMA-7, 10 months for BELINDA, and 6 months at the time of publication of TRANSFORM. The complete response [CR] rate to CAR T-cell therapy in ZUMA-7 was 65%, and the CR rate with ASCT was 32%.4 With BELINDA there were no difference between the 2 groups, a CR of 28% [in each arm],5 and with TRANSFORM [the liso-cel had a] 66% CR rate which is identical to ZUMA-7 and 39% with ASCT.6

Two of the studies were positive, the third one is negative. If you want to know why is the third one was negative, is it a question of product, is it a question of trial design, is it a question of delays in manufacturing the product? I think there were many explanations raised. I personally think there was not one single explanation; it was a mixture of different explanations. Tisa-cel [is an effective] primary CAR T-cell therapy for children with acute lymphoblastic leukemia, so its a good [therapy], but in this DLBCL setting it may be inferior, and there are some data from a registry study coming from [France] suggesting that it is inferior to axi-cel.7

[For ZUMA-7, the PFS [progression-free survival] rate at 24 months was 46% for axi-cel versus 27% for ASCT.4 In BELINDA [PFS data were] not provided, [so PFS in both arms were] not reached,5 and [for TRANSFORM] we have a 12-month PFS rate of 50% vs 33%, so a highly significant difference for 2 [of these trials].6 So its a significant change for early relapse, and potentially for later [relapse].

REFERENCES

1. NCCN. Clinical practice guidelines in oncology. B-cell lymphomas, version 2.2023. Accessed March 23, 2023. https://bit.ly/3TEXEqA

2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed March 23, 2023. https://bit.ly/3ngfNPF

3. FDA approves lisocabtagene maraleucel for second-line treatment of large B-cell lymphoma. News release. FDA. June 24, 2022. Accessed March 23, 2023. https://bit.ly/3TBFcPE

4. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

5. Bishop MR, Dickinson M, Purtill D, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022;386(7):629-639. doi:10.1056/NEJMoa2116596

6. Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6

7. Bachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma.Nat Med. 2022;28(10):2145-2154. doi:10.1038/s41591-022-01969-y

See the article here:
When to Use Second-Line CAR T-cell Therapy for Relapsed ... - Targeted Oncology

Updates on Recent Advances and Treatments for Hematologic … – Targeted Oncology

With the increasing frequency of almost all diseases covered by hematologic malignancies, many questions and new ideas are constantly being answered and addressed for patients and physicians. As a result, a 2-day symposium, the Summit of the Americas on Immunotherapies for Hematologic Malignancies, was created to provide an overview of the most recent advances in hematologic oncology.

During the meeting, 25 experts joined director of the Summit of the Americas on Immunotherapies for Hematologic Malignancies, Guenther Koehne, MD, PhD, for the opportunity to discuss and learn about some of the new developments in the treatment of patients with leukemia, lymphoma, multiple myeloma, and stem cell transplantation and more.

Presentations highlighted at this year's meeting included discussions on several novel immunotherapies, new combinations, and even updates on the evolving field of molecular-based therapies.

The reason why we have this summit is to update physicians and faculty members on the new developments in the field. Immunotherapies are developing relatively fast, and we are all excited about the implementation of these immunotherapeutic approaches, Koehne, deputy director and chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida, said in an interview with Targeted OncologyTM.

In the interview, Koehne provided an overview of The Summit of Americas on Immunotherapies for Hematologic Malignancies and some of the recent and exciting advances being seen in the hematology space.

Targeted Oncology: Can you explain the purpose of The Summit of Americas on Immunotherapies for Hematologic Malignancies?

Koehne: The title of the conference gives away a little bit. It's a global summit on immunotherapies for hematologic malignancies. The reason why we have this summit is to update physicians and faculty members on the new developments in the field. Immunotherapies are developing relatively fast, and we are all excited about the implementation of these immunotherapeutic approaches.

In all diseases that are covered by hematologic malignancies, that is acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, multiple myeloma, each of these diseases have specific drugs or combinations of drugs with an antibody that can specifically target tumor cells without targeting healthy cells, which wouldn't be the case with chemotherapy and chemotherapy combinations that we've been given before. Now, with the rapid development, there are so many questions that we've tried to answer or at least address. We cannot answer all of them because of the rapidity of the development. But for example, is 1 immunotherapeutic drug enough to get the patient into long lasting remission? Or should we combine them, or should we sequence them? Then there's still the follow-up question of when to provide the patient or send them for a stem cell transplantation, which would be an autologous stem cell transplantation for multiple myeloma or donor-derived allogeneic stem cell transplantation for patients with leukemia. As of now, that is still the only curative therapy that we have.

We also know that the patients should be in a complete remission. Particularly now we have very sensitive tests that we summarize as minimal residual disease, MRD, testing. We know that patients that are MRD-positive before an allogeneic stem cell transplant for acute myeloid leukemia, do as well as those that are MRD-negative. Now with these new approaches and targeted therapies, we are trying to get them into a complete remission before sending them to the allogeneic stem cell transplantation. All these topics are addressed [at this meeting] and they are important to answer.

What ongoing research has recently caught your eye in the hematology field?

I'm the principal investigator for a lot of new clinical trials specifically addressing FLT3-mutated acute myeloid leukemia, TP53-mutated myeloid leukemia, and I have a lot of trials in the workup for multiple myeloma. I'm leading 1 exciting clinical trial now that for the first time utilizes the CRISPR technology, which is molecular silencing and therefore down regulating the CD33 expression on hematopoietic stem cells. With that, we can now transplant patients with acute myeloid leukemia with CD33-negative hematopoietic stem cells. One may ask, why is that important? Because CD33 is also expressed on leukemia cells. The reason why we cannot target specifically acute myeloid leukemia with CAR T cells, or with any specific CD33 targeting antibodies, is that you would also target the healthy hematopoietic stem cell at the same time.

To prevent this, we can downregulate and transplant the patient with CD33-negative stem cells, and everything that is left after transplantation expressing CD33 is then the leukemia cells. With that, we have a specific targeting approach for this patient population as well. We have successfully transplanted 3 patients with these CD33-negative stem cells, and we can prove at this point that it's safe. We can follow up with immunotherapies for these patient populations, and that is clearly exciting and accompanied new levels of immunotherapeutic approaches in our view.

Wonderful, and are there any other future advances in the hematologic malignancy field that you're excited about?

Multiple myeloma has a lot of interesting developments right now with the so-called bispecific antibody treatments of the CAR T-cell treatments, specifically, in this case, targeting the B-cell maturation antigen or BCMA. That will lead to long-term maintenance of remissions.

I believe that will also add this topic of the discussion here at this meeting now, because with the CAR T cells or bispecific antibodies that specifically get the patients into a remission again, what is the role of autologous stem cell transplantation? In this scenario, do we still need autologous transplant or what would be the best timing for autologous stem cell transplantation in patients with multiple myeloma? It is an ongoing discussion. I personally believe that autologous stem cell transplantation still has a good and important role in maintaining a long-lasting relationship with these patients, with the CAR T cells that we have, or with the bispecific antibodies that we have and we can bring patients back into remission.

These remissions have a limited duration, so that indicates to me that 1, achievement of the complete remission patient should then be consolidated with autologous stem cell transplantation, which leads to more transplants than we had before because you don't transplant patients if they don't necessarily have a good remission.

Read more from the original source:
Updates on Recent Advances and Treatments for Hematologic ... - Targeted Oncology