Category Archives: Cell Therapy

Repeat infusions of naive immune B-cells were safe and delayed disease onset, reduced disease severity, and extended survival in animal models of amyotrophic lateral sclerosis (ALS), a study found.

The approach was also deemed safe in the treatments first in-human case study, in which it eased disease severity and reduced biomarkers of inflammation in a person with advanced ALS.

We were able to show safety and efficacy, as well as how the B cell therapy worked in mice, and we demonstrated that our approach was safe and feasible in a human, senior author Mark C. Poznansky, MD, PhD, an attending physician at Massachusetts General Hospital (MGH) and a professor of medicine at Harvard Medical School, said in a hospital press release.

Details of the potential new B-cell therapy were published in The FASEB Journal in the study, Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.

This is a first study of its kind to apply B cells to the treatment of ALS and sets us up for a trial of this new treatment approach to a currently incurable disease, said Poznansky, who is also the director of the Vaccine and Immunotherapy Center at MGH.

Elevated inflammation is known to play a role in the onset and progression of ALS, a condition marked by the loss of motor neurons, the nerve cells that control certain body movements.

Mitigating neuroinflammation via immune targeting may provide an effective therapeutic strategy for attenuating neuronal loss in ALS, the researchers wrote.

B-cells are best known as the immune cells that produce antibodies to protect the body from infections and other harmful substances. But recent research has demonstrated that these cells can also respond to tissue injury, help rebalance immune function, and coordinate tissue repair.

Previous work by lead author Ruxandra F. Srbulescu, PhD, assistant professor of neurology at Harvard Medical School, showed that naive B-cells reduced inflammation and promoted recovery in mice with skin or brain injuries.

These benefits were driven by a process the team dubbed pligodraxis, in which B-cells can adopt immunoregulatory and neuroprotective properties.

What we observed early on in preclinical studies has been a remarkable effect of B cells in the context of brain lesions both brain structure and function were protected by treatment with these cells, which made us consider applying them as a therapeutic in the context of neurodegenerative disease, Srbulescu said.

A team led by Srbulescu and Poznansky tested this type of B-cell therapy in an ALS mouse model and, for the first time, an individual with ALS.

The ALS mouse model carried mutations in the SOD1 gene, a known ALS-related gene. The mice received 10 weekly doses of mature naive B-cells isolated from the spleens of donor mice, administered directly into the bloodstream.

Results showed that the B-cell treatment was safe and significantly delayed disease onset compared with a control treatment. Treated animals also tended to have better neurological function, indicating less severe disease, and a longer survival time, though the differences between groups failed to reach statistical significance.

Tissue analyses showed significantly less abnormal or dying motor neurons, as well as reduced markers of neuroinflammation.

We were able to show that B cells, which can be readily obtained from the blood, could treat ALS in a well-established mouse model of the disease, and we obtained permission from the US Food and Drug Administration and our hospital to try this treatment approach in an individual with ALS, Poznansky said.

The participant was a man in his 50s who received a diagnosis of ALS following the onset of bulbar symptoms, which affect the muscles of the face, jaw, and throat, impairing speech and swallowing. He was being treated with the standard ALS treatment riluzole (sold as Rilutek, among other brand names).

B-cells were collected from the participants adult child, who was an immunological match, and infused into the patients bloodstream twice, 60 days apart. This was deemed was safe and did not trigger an abnormal inflammatory response.

After the first infusion, the patient had a modest improvement in scores on the revised ALS Functional Rating Scale (ALSFRS-R), an assessment of disease severity that measures the ability to perform everyday activities.

After the second infusion, the participants ALSFRS-R score again improved but gradually declined, as expected in ALS, thereafter. The participant withdrew from the study on day 136.

Blood tests showed marked treatment-related reductions in markers for body-wide inflammation and in pro-inflammatory immune cells.

Still, levels of neurofilament light chain, a marker of nerve cell damage, continued to rise, suggesting that the intervention at a relatively late/end stage of disease progression would be insufficient to halt neurodegenerative processes, the researchers wrote.

A Phase 1 trial will be needed to further evaluate the safety and efficacy of this novel approach to treating ALS, the researchers concluded. Such a trial is now in the planning stage, Poznansky said.

Continued here:
New B-cell therapy eases disease severity, delays onset: Study - ALS News Today

Hot on the heels of receiving the FDAs coveted Regenerative Medicine Advanced Therapy (RMAT) designation for its Lomecel-B product, Longeveron this week revealed its lead cell therapy has also been granted Fast Track designation for the treatment of mild Alzheimers. The Miami-based biotech has now received five different FDA designations for Lomecel-B, and this latest one should help streamline its development and expedite its review as a potential Alzheimers therapy.

The Fast Track designation comes on the back of compelling Phase 2 trial results, which demonstrated that Lomecel-B slowed or prevented the progression of Alzheimers in some groups of patients with the mild form of the disease. Longeverons aim is now to move the therapy into the next phase of trials in Alzheimers as soon as possible, potentially as early as next year. But the company is not putting all its eggs in one basket

Longevity.Technology: Derived from the bone marrow of young, healthy adult donors, Lomecel-B, a so-called living cell product, has demonstrated pro-vascular, pro-regenerative and anti-inflammatory effects. With multiple mechanisms of action, the drug is being explored for its potential in several indications, spanning neurodegeneration, frailty and heart conditions. Could we be looking at a longevity drug in the making? To learn more, we caught up with Longeveron CEO, Wael Hashad.

Longeveron was founded with a mission to target age-related diseases, which are often characterized by chronic inflammation, combined with a decline in immune system and blood vessel function. The companys approach involves building therapeutics, like Lomecel-B, from special living cells called medicinal signaling cells (MSCs) derived from donated bone marrow tissue.

One of the key mechanisms through which MSCs exert their therapeutic benefits is by releasing exosomes, growth factors and other proteins, such as anti-inflammatory cytokines, which have the potential to significantly reduce inflammation, while stimulating the promotion of regenerative and repair responses. This is why, rather than targeting amyloid plaques or neurofibrillary tangles, Longeveron is going after the inflammation of the central nervous system that is increasingly recognized as a driver of neurodegeneration in Alzheimers.

With preliminary clinical data showing that Lomecel-B simultaneously targets multiple aging-related processes, Hashad explains that an important part of the recent Phase 2 Alzheimers trial was demonstrating these effects in humans.

We wanted to see if there was any data supporting the hypothesis of the mechanism of action, which is the anti-inflammatory and pro-vascular effect of the drug, he says. So, in addition to other clinical scales that you typically use in Alzheimers trials, we also added MRI measurement of brain volumes, which is a very objective exploratory endpoint.

This means that, in addition to study results showing that Lomecel-B was safe, well-tolerated, and demonstrated statistically significant improvements in specified cognitive function measurements in certain groups, Longeveron also generated some compelling MRI data.

We got a big, positive surprise from the effect that we saw on the MRI, which indicated that there was less shrinkage in the brain compared to placebo, says Hashad. And that was significant, not just on the total volume of the brain, but also on the hippocampal volume, which is the memory formation center of the brain.

This data, Hashad believes, was instrumental in the company receiving the recent designations from the FDA, which should help accelerate the process to move Lomecel-B forward as a potential treatment for mild Alzheimers.

Recent FDA guidance for Alzheimers disease indicates that clinical trials showing an effect on a surrogate endpoint that is determined to be reasonably likely to predict clinical benefit can be the basis for accelerated approval. The MRI data from the Phase 2 trial, which can be considered a surrogate endpoint, may significantly expedite the development and approval process for Lomecel-B.

We can now have a much more active dialogue with the FDA, and potentially discuss the possibility of an accelerated approach to bring the product to the market using surrogate endpoints, for example, he says. The next step is to meet with the FDA before the end of the year to talk about the blueprint for the next phase of development.

With chronic inflammation also heavily implicated in many other age-related conditions, Longeveron believes that the anti-inflammatory, pro-vascular mechanism of Lomecel-B can also play a role beyond the brain.

We have an indication that Lomecel-B may work by reducing levels of inflammation, and also improving the health of the vascular system and therefore the blood supply and the blood flow to the brain and other areas of the body, says Hashad.

In addition to its program in Alzheimers, Lomecel-B is also being explored as a treatment for age-related frailty, as well as a congenital heart condition called hypoplastic left heart syndrome (HLHS).

Age-related frailty, or sarcopenia, is thought to affect around 15% of individuals aged 65 and older, and significantly heightens the risk of adverse clinical outcomes from disease and injury. Despite its prevalence, no medical treatments for the condition have been approved by the FDA or any other regulatory body.

Longeveron has commenced multiple clinical trials of Lomecel-B in frailty but has faced some challenges in terms of determining the endpoints needed to demonstrate efficacy to the FDA.

We have seen good data in our studies, but there is no product approved for aging related frailty, and were still trying to get an agreement with the FDA on what that indication is, says Hashad. So far, what we have used in our trials is the six-minute walk test, which evaluates the distance a patient can walk within six-minutes. We have seen a statistically significant improvement in our Phase 2 study with this metric at nine months. We will continue to work with the FDA which also wants to see a more objective assessment as well, so were trying to get alignment on that before we proceed forward on that program.

Longeverons more recent work in cardiology is of keen interest to the companys founder, the renowned cardiologist Dr Joshua Hare. While the program is currently focused on a rare, inherited condition, Hashad admits that the company is exploring the potential to target other heart-related indications.

There are certain things that were working on that I cannot disclose at this time, he says. But cardiology remains one of Joshs biggest passions, and we believe that Lomecel-B may have multiple potential applications within the heart disease area as well as other products that were also working on.

So, if Lomecel-B goes on to prove successful in multiple age-related diseases, would that make it a potential longevity drug? Hashad doesnt bite, although he does believe the therapy could have more applications in other diseases.

As a startup, we must focus on the work that we currently have at hand, but hopefully, as we continue to advance our work and grow, then we can embark on other areas of disease that can also benefit patients in the future, he says. There is no doubt that life expectancy is increasing around the world the question is how we ensure that people are not just living longer but living longer with a better quality of life, whether by improving their heart health, muscle health, or brain health. We believe that Lomecel-B, and the other products that were working on in our labs, can potentially help to improve that quality of life.

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Cell therapy shows potential in multiple age-related diseases - Longevity.Technology

When Mindy's previous treatment stopped working for multiple myeloma, she opted for CAR-T cell therapy.

Following an infection that was resistant to treatment and a few extra blood tests, the doctor advised me to see a hematologist (that was OK!) or an oncologist (not so good to hear). In January 2007, the diagnosis of multiple myeloma was followed by several new normals for my family and me.

Let the journey begin. What is myeloma? How do my husband and I tell and support my daughters (one finishing high school and the other in college)? How do I support my husband? Will I survive this? Who will be there to support me? What treatments will I need? Can I trust my doctor to provide the best treatment for me? Who are all these strange people in the clinic? What about my friends? My co-workers? Would they treat me the same? Who will understand what I am going through? After letting the diagnosis set in, while I was ready to fight this battle, I did not realize what a challenge this would be. I was faced with so many factors out of my control.

Fast forward 16 years. It took lots of energy, questioning, researching and talking. Some of my questions and fears were addressed, but new ones were constantly popping up. I remained in the working world for more than 13 years, sometimes walking from my office building to Massey Cancer Center in Richmond, Virginia for treatment. One autologous (my stem cells) transplant. One allogeneic (donor) transplant. Yes, I am now my brother! And thank goodness for my brothers loving generosity. Seven years of partial remission after transplants. What happened during these 16 years? Too many times, I heard that my numbers were stable followed by the news that my numbers were slowly climbing. More treatment regimens. It was an emotional roller coaster as I moved forward.

I cherished amazing inspiration, support and laughs from my dear family, my health care team, friends and other myeloma colleagues. I had completed several half-marathons to support The Leukemia & Lymphoma Society; organized and co-led a local International Myeloma Foundation support group; and volunteered at Massey Cancer Center. These activities kept me connected with my community, others who were impacted and it raised my resiliency.

The best celebrations enriching my life that I never expected was witnessing my daughters become beautiful, caring, compassionate, strong professional women; becoming a mother-in-law; and then becoming a grandmother! Life goes on in beautiful ways. For this, I am grateful.

In 2023 after two years of a specific treatment regimen that kept my numbers stable that tricky myeloma figured out a way to stump us again. Now what? CAR-T cell therapy? Bispecific antibodies? How grateful that I have options, but still anxious moving forward. I chose CAR-T cell therapy for the one and done option. The beginning of my CAR-T cell therapy journey was a little scary and only a bit bumpy. But, it was well worth the effort to power through! Twelve months after CAR-T cell therapy, I am still in complete remission and living my best life!

My favorite sayings during my journey have been This too shall pass and It is what it is. If I could use two words to describe my journey, they are hope and resilience. How are hope and resilience part of your story?

This post was written and submitted byMindy C. Fast. The article reflects the views ofFastand not of CURE. This is also not supposed to be intended as medical advice.

For more news on cancer updates, research and education, dont forget tosubscribe to CUREs newsletters here.

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My Decision to Receive CAR-T Cell Therapy for Multiple Myeloma - Curetoday.com

Blocking the TGF- signalling pathway produced effective antitumour activity against hepatocellular carcinoma.

Scientists at the University of California San Diego have discovered that genetically modified NK-cell therapy improves the targeting and treatment of hepatocellular carcinoma (HCC), the most treatment-resistant form of solid tumour.

Unlike chimeric antigen receptor (CAR)-expressing T-cell therapy, the NK treatment does not require personalisation, meaning it could be mass produced and shelf-ready for patients to begin therapy without delay. Dr Dan Kaufman, lead study author and director of the Sanford Advanced Therapy Center, explained: To some extent all tumour cells perhaps hepatocellular carcinoma more so inhibit immune cells that try to kill themThis is one key reason why some immunotherapies like CAR T cells have been less successful for solid tumours than for blood cancers the immunosuppressive tumour microenvironment.

The researchers produced stem cell-derived NK cells in which the receptor for transforming growth factor beta (TGF-) was disabled. The liver and HCC tumours contain a high amount of TGF-, which inhibits immune cell activity and enables cancer to grow. It was discovered that typical NK cells without the disabled receptor, like CAR T cells, were not effective in destroying the cancer. When they assessed the modified NK cells, Dr Kaufman stated: we got very good antitumour activity and significantly prolonged survival.

These studies demonstrate that it is crucial to block transforming growth factor beta at least for NK cells, but I also think its true for CAR T cells, Dr Kaufman added. If you unleash NK cells by blocking this inhibitory pathway, they should kill cancer quite nicely.

In the future, Dr Kaufman believes their findings will aid clinical trials of numerous research groups and companies, whether they study CAR T-cell or NK-cell therapies and tackle hepatocellular carcinoma or other difficult types of solid tumours. He concluded: Anyone developing such therapies for solid tumours should be working to inhibit transforming growth factor beta activity to improve cancer-killing and attain effective anti-tumour activity.

This study was published in Cell Stem Cell.

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Treating HCC with genetically modified NK-cell therapy - Drug Target Review

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Excerpt from:
Designing drug delivery systems for cell therapy - Nature.com

Taiga Nishihori, MD, senior member in the Blood & Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center, discusses a study in which investigators evaluated patients with relapsed and/or refractory (R/R) multiple myeloma who were hospitalized and treated with commercial ciltacabtagene autoleucel (cilta-cel; Carvykti) at Moffitt Cancer Center between May 2022 and May 2023.

Patients in the initial group to be evaluated were given lymphodepleting chemotherapy as outpatient, followed by chimeric antigen receptor (CAR) T-cell infusion as inpatient. Patients were also monitored, then discharged to an outpatient immune cell therapy service. The first 30 days post-infusion was the focus of the study.

Transcription:

0:09 | We wanted to look at our experience on treating patients with multiple myeloma who received cilta-cel, which is a CAR T-cell [therapy]. We started looking at this in 2022. Initially, we started doing an outpatient model, which was the beginning of it, and then we changed it to inpatient. The chemotherapy was given, lymphodepletion in particular, and chemotherapy was given as an outpatient; they readmitted patients. But then, we quickly realized that patients who are in the hospital were basically spending a lot of time waiting for toxicity to occur. We changed our approach entirely outpatient. And then we looked at over 20 patients who received those. We also demonstrated that the amount of time they spend in a hospital has been cut down from 11 days to a median of 4 days.

1:11 | We wanted to look at the hospital duration. We also wanted to look at the outcomes of this approach. We have established our system to take care of patients, mostly on the outpatient side. The patients are seen daily in what is called 3 central outpatient areas, and we have managed to conduct this safely as an outpatient.

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Study Focuses on Outpatient CAR T-Cell Therapy in Multiple Myeloma - Targeted Oncology

Pluris newly launched CMDO business will manufacture two novel cell therapy product candidates for Kadimastem.

On July 18, 2024, Israel-based biotechnology company, Pluri, announced that it has signed a tech transfer and manufacturing agreement with Kadimastem, an Israel-based clinical stage biotechnology company developing therapeutic cells to treat amyotrophic lateral sclerosis (ALS) and diabetes. Under the agreement, PluriCDMO, Pluris contract development and manufacturing organization (CDMO) business launched in January 2024 (1), will manufacture two cell therapy product candidates for Kadimastem at its 47,000-ft2 good manufacturing practice (GMP) cell production facility at its MATAM Advanced Technology Park site in Haifa, Israel (2).

The two cell therapy product candidates from Kadimastem are AstroRx, clinical-grade human astrocytes (nervous system supporting cells) for the treatment of ALS, and IsletRx, clinical-grade pancreatic islet cells that produce and secrete insulin and glucagon in response to blood glucose levels. The material PluriCDMO produces for AstroRx will supply an upcoming FDA Phase II study. Meanwhile, IsletRx is in development for treating diabetes.

Working with Pluri marks a pivotal milestone, enhancing Kadimastems capacity to manufacture our products under GMP conditions, said Ronen Twito, executive chairman and president of Kadimastem, in a company press release. This collaboration is integral to our strategy as we prepare for clinical trials and expand into the US market with our AstroRx product candidate.

Kadimastems decision in selecting PluriCDMO is based on Pluris expertise and experience in developing and manufacturing GMP-grade cell-based products for clinical use. The CDMO has the capacity to scale up from initial clinical trial batches to mass-scale commercial production, according to Pluri in the press release.

Pluris CDMO division offers access to its patented bioreactor system, which enables 3D cell expansion at mass scale using a fully controlled, automated, and validated process. The companys 3D cell expansion technology supports the large-scale growth of cells and offers unique batch-to-batch consistency in a scalable, cost-effective manner that can support late-stage clinical trials in key jurisdictions, including FDA, the European Medicines Agency, Israelis Ministry of Health, Japans Pharmaceuticals and Medical Devices Agency, and the Ministry of Food and Drug Safety of the Republic of Korea. In addition, the companys PluriMatrix technology enables industrial-scale production of cell-based products (1).

We are excited to work with Kadimastem and support their development of cell therapies, potentially improving the lives of patients with ALS and diabetes, said Yaky Yanay, chief executive officer and president of Pluri, in the press release. This collaboration underscores the versatility of our PluriCDMO platform and our commitment to aiding innovative companies in advancing their life-saving therapies. We look forward to a successful collaboration with Kadimastem as they make progress with their clinical development programs.

Kadimastem specializes in developing allogeneic (i.e., off-the-shelf) proprietary cell products based on its technology platform, which enables the expansion and differentiation of human embryonic stem cells (hESCs) into functional cells.

1. Pluri. Pluri Launches Advanced Global Cell Therapy Contract Development and Manufacturing Organization. Press Release, Jan. 8, 2024. 2. Pluri. 10KAnnual 2023 Financial Report. http://www.sec.gov. Sept. 12, 2023.

Source: Pluri

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Pluris CDMO Business to Manufacture Cell Therapy Candidates from Kadimastem - BioPharm International

FDA Grants Fast Track Designation to ADI-270 for Pretreated Advanced ccRCC

A fast track designation has been granted by the FDA to ADI-270 as a potential therapy option for patients with metastatic or advanced clear cell renal cell carcinoma (ccRCC) previously treated with an immune checkpoint inhibitor and a VEGF inhibitor.1

ADI-270 is an allogeneic, off-the-shelf, CD70-targeted gamma delta CAR T-cell therapy candidate. It is directed toward CD70 using the natural CD27 receptor and features a dominant negative form of the transforming growth factor- receptor II intended to deliver functional resilience to the immunosuppressive tumor microenvironment. Furthermore, ADI-270 is intended to increase exposure and persistence by reducing susceptibility to graft-vs-host elimination.

We are pleased that ADI-270, our first ever gamma delta 1 CAR T-cell therapy candidate to enter clinical trials for solid tumors, has been granted fast track designation by the FDA, Chen Schor, president and chief executive officer of Adicet Bio, stated in a news release. ccRCC is the most common type of kidney cancer, and this significant milestone underscores our commitment to advancing innovative treatments to these patients as quickly as possible.

Findings from preclinical studies presented at the 2023 American Society of Gene + Cell Therapy Annual Meeting showed that ADI-270 successfully generated and expanded without indications of fratricide. The agent also displayed a less-differentiated T-cell memory phenotype with low expression of exhaustion markers; potent in vitro cytotoxicity; and favorable cytokine and chemokine profiles.2

Additionally, ADI-270 generated highly potent tumor growth inhibition via xenografts in immunodeficient mice. Furthermore, selective T-cell infiltration, proliferation, and activation were observed within the tumor.

A phase 1/2 trial (NCT06480565) will investigate ADI-270 in patients at least 18 years of age with histologically or cytologically confirmed ccRCC who have documented evidence of advanced or metastatic disease. Prior treatment with an immune checkpoint inhibitor and a VEGF inhibitor is required; notably, the VEGF inhibitor must have been given in the advanced/metastatic setting. Other key inclusion criteria include at least 1 measurable target lesion per RECIST v1.1 criteria and a Karnofsky performance status of at least 70. Patients will need to be at least 3 weeks or 5 half-lives removed from their last dose of prior therapy.3

The study will exclude patients with central nervous system (CNS) metastases or spinal cord compression, unless they have finished treatment and discontinued corticosteroids for at least 8 weeks and remain stable prior to enrollment. Other key exclusion criteria include clinically significant CNS dysfunction; prior radiation therapy within 21 days prior to start of study treatment, except for palliative radiotherapy to bone lesions completed at least 2 weeks prior to the first study treatment; prior gene therapy, genetically modified cell therapy, or adoptive T-cell therapy within 6 weeks of enrollment; and any prior treatment with a CD70-targeted therapy.

The trial will also exclude patients with an active malignancy within the past 24 months, other than RCC; definitively treated basal or squamous cell carcinoma of the skin; or carcinoma in-situ of the cervix or bladder. Patients with any primary immunodeficiency or active autoimmune disease requiring ongoing systemic immunosuppressive therapy will also be excluded.

Enrolled patients will undergo lymphodepletion with fludarabine plus cyclophosphamide prior to receiving a single dose of ADI-270. During dose escalation, ADI-270 will be given at ascending dose levels to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Dose expansion will further evaluate the CAR T-cell therapy at the MTD/MAD.

The primary end points of the study are the incidence of dose-limiting toxicities and the proportion of treatment-emergent and -related adverse effects.

References

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FDA Grants Fast Track Designation to ADI-270 for Pretreated Advanced ccRCC - http://www.oncnursingnews.com/

Once a month, Talaya Reid wakes up early to board a flight from Philadelphia to Boston, in hopes of impacting research into lupus and the potential benefits of chimeric antigen receptor (CAR) T cell therapy to treat the chronic autoimmune disease.

Reid travels to UMass Chan Medical School in Worcester to participate in an individualized clinical research study exploring the use of CAR T cell treatment in lupus nephritis for severe or nonresponsive lupus. The Lupus Center at UMass Chan is one of five national sites participating in the trial sponsored by Kyverna Therapeutics. Reid is one of a dozen patients in the United States to have undergone CAR T cell treatment for lupus.

Ive participated in treatments before that have calmed my lupus symptoms down, but the symptoms were still there, or the treatments did nothing at all. When I heard it was possible to live without lupus symptoms or flare ups anymore, I was very interested in participating in this trial, Reid said.

Roberto Caricchio, MD, theMyles J. McDonough Chair in Rheumatology, professor of medicine, chief of the Division of Rheumatology in the Department of Medicine and director of the Lupus Center at UMass Chan, is principal investigator of the CAR T cell therapy trial in lupus at UMass Chan.

This treatment is not for everyone. It is for those patients who unfortunately have gone through several treatments that we have available and somehow the lupus does not seem to be matched by them. Its a significant, but restricted group of patients. And within that group of patients, it takes a special individual who is looking for something different and commits to something new, Dr. Caricchio said.

Lupus is a chronic autoimmune disease that involves multiple organ systems and often requires lifelong treatment with immunosuppressive or immunomodulatory drugs, which are not effective for all patients. Lupus nephritis is a complication of lupus that causes inflammation of the kidneys, impacting the bodys ability to remove waste from the blood or regulate body fluids.

"Ive participated in treatments before that have calmed my lupus symptoms down, but the symptoms were still there, or the treatments did nothing at all. When I heard it was possible to live without lupus symptoms or flare ups anymore, I was very interested in participating in this trial."

CAR T cell therapy has been recognized as a significant advancement in treating cancers such as leukemia, lymphoma and more recently, multiple myeloma. CAR T cells are created by removing some of a patients white blood cells, including immune system T cells, and genetically altering them in a lab to produce CARs. These changes help the patient's T cells identify and kill antigens on the outside of the harmful cells once they are put back into the body.

Reids first treatment in March required a two-week hospital stay, during which she underwent lymphodepletion chemotherapy and an infusion of her CAR T cells and was monitored by medical personnel in the Blood and Marrow Transplant program at UMass Memorial Medical Center. She stayed in the Worcester area for three weeks after her discharge from the hospital before transitioning to monthly visits.

Each monthly visit to the Lupus Center at UMass Chan requires an assessment by a trained provider and extensive bloodwork at UMass Memorial Medical Center-Memorial Campus. During her day-long visit, Reid has more than 15 vials of blood taken. The blood samples are separated into two categories: for future Lupus research and for understanding what the CAR T cell therapy treatment is doing for her.

Once her bloodwork is completed, Reid travels back to Boston to catch a plane home to Philadelphia.

If her lupus symptoms havent flared up again, she will only need to come to Worcester for one visit in 2025. She will continue to be observed by the Lupus Center at UMass Chan for at least two years.

As of now, I can say that this is the best I've ever felt. I feel really good, said Reid, 28, a pharmaceutical scientist from Fairless Hills, Pennsylvania, who was diagnosed with lupus at 22. She said her flares previously ranged from minimalfatigue or discomfortto major, with joint pain and/or migraines that impacted her ability to attend college classes or work.

According to Caricchio, the Lupus Center has enrolled a second patient in the CAR T cell therapy trial who is expected to begin treatment in July.

This treatment not only helps the patients currently participating in these trials, but also future patients, Caricchio said. It has been a very strong learning experience. The plus is that this type of treatment isnt only groundbreaking but will also teach us a lot about lupus itself as a disease and we will be able to capitalize on that and find better ways to help patients.

Caricchio cautioned that all results are preliminary, saying, It is important to remember that this is an experimental treatment and therefore only upon completion of the clinical trial will we know if this approach is truly transformative for lupus patients.

The Lupus Center is led by Caricchio and Elena Gkrouzman, MD, assistant professor of medicine, and includes a team of dedicated experts, including rheumatologists, dermatologists and nephrologists, as well as clinical research coordinators.

The CAR T cell therapy clinical trial at the Lupus Center at UMass Chan is conducted in collaboration with the Cancer Research Office at the UMass Cancer Center; the Blood Cancer Center physicians and teams, including Jan Cerny, MD, PhD, associate professor of medicine; Muthalagu Ramanathan, MD, professor of medicine; and Poorva Bindal, MD, assistant professor of medicine; and the Divisions of Hematology/Oncology and Renal Medicine/Nephrology.

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Lupus Center at UMass Chan investigating CAR T cell therapy for severe or nonresponsive lupus nephritis - UMass Medical School

Sarcoma is a type of cancer that affects the body's connective tissue, and as such can appear in any part of the body where this type of tissue is found.1 According to the Sarcoma Foundation of America, sarcoma constitutes 15% to 20% of all cancers in children, but is relatively rare in adults, for whom it constitutes 1% of cancers.

In about half of cases, sarcoma is incurable with currently available treatments, including surgery, chemotherapy, and radiation therapy. As such, great unmet need remains for patients with sarcoma.

An important area of interest for new therapeutic development in sarcoma is cell/gene therapy, which a number of companies and academic institutions are now pursuing. In honor of Sarcoma Awareness Month, observed annually in July by the patient and clinician communities, CGTLive is taking a look back at the progress that has been made for cell/gene therapy candidates in sarcoma over the past year. Click the "READ MORE" buttons for more details and information about each item.

June 5, 2024 The IGNYTE-ESO (NCT03967223)substudy 2 evaluating letetresgene autoleucel (lete-cel; Adaptimmune) in patients with synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) met its primary endpoint of safety and efficacy at a planned interim analysis, with a 40% overall response rate in evaluable participants.

Data from the substudy were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 - June 4, in Chicago, Illinois, by Sandra P. DAngelo, MD, sarcoma oncologist, cellular therapist, and associate attending physician, Memorial Sloan Kettering Cancer Center.

[These data] support the potential of lete-cel as a novel therapy for patients with advanced or metastatic SS and MRCLS. The primary analyses will be presented late 2024 (sic). Further analyses of translational correlates are pending, DAngelo said during her presentation.

May 11, 2024 CCNG1-targeted Deltarex-G gene therapy plus an FDA approved drug (Deltarex-G+) showed some evidence of response in patients tumors, including pancreatic cancer, breast cancer, and sarcoma. All tested tumors had enhanced CCNG1 expression.

Data from the BLESSED expanded access study (NCT04091295) were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Erlinda Gordon, MD, founder and president, Aveni Foundation, and director, biological and immunological therapies, and chairman, institutional biosafety committee director, Cancer Center of Southern California/Sarcoma Oncology Center, and founder, chief operating officer, and FDA liaison, Counterpoint Biomedica.

Deltarex-G is the only tumor targeted gene therapy that can be injected intravenously and it in vivo gets into the tumor microenvironment by binding to abnormal signature proteins in the tumor. So, it's unlike the ex vivo gene therapies for cancer... it's an off the shelf gene therapy product that has a navigation system that goes to the tumor itself, Gordon told CGTLive during the meeting. We tested that... CCNG1 is present in all the tumor types that we have tested including sarcoma, pancreatic cancer, breast cancer, testicular cancer, bladder cancer, so that we think it's a tumor agnostic therapy, rather than looking for a very rare oncogene to target."

February 22, 2024 Modified natural killer (NK) cells (IL1RAP CAR NK, TGFi-NK, IL1RAP CAR CXCR2 NK) demonstrated enhanced antitumor activity alone and combined with NKTR-255 and dinutuximab against Ewing Sarcoma (ES) tumor cells in vitro, providing rationale for further preclinical study of these cells.

The preclinical data were presented by Wen Luo, PhD, assistant professor, Pediatrics and Pathology, New York Medical College, at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024.

ES is a malignant pediatric bone associated sarcoma and it is characterized by fusion oncogene in EWS/FLI. Patients with localized ES have around 75% 5-year overall survival (OS) but for patients with metastatic disease, they only have a dismal outcome of around 30% 5-year OS, and patients with relapsed/refractory disease have only 5% 6-month event-free survival. Current treatment including surgery, radiation, and chemotherapy have failed to improve patient outcomes for decades, so novel therapeutics strategies are urgently needed, Luo said during her presentation.

February 2, 2024 Adaptimmune Therapeutics biologics license application for afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), an investigational T-cell receptor (TCR) T-cell therapy intended to treat SS, has been accepted by the FDA with priority review. The Prescription Drug User Fee Act (PDUFA) target action date has been set for August 4, 2024.

The FDAs acceptance of the BLA submission brings us onestep closer to redefining treatment for people with SS, Adrian Rawcliffe, BSc, the chief executive officer of Adaptimmune, said in a statement.Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-celthe first engineered T-cell therapy on the market for a solid tumor cancer.

Afami-cel targets MAGE-A4-expressing solid tumors. It is delivered as a single-dose, and intended to treat patients with advanced SS. The majority of patients who are treated with current standard of care therapy for advanced SS experience disease relapse and in many cases they are left with no further FDA-approved treatment options after receiving multiple lines of therapy.

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Sarcoma Awareness Month 2024: Looking Back at a Year of Progress for Cell and Gene Therapy - CGTLive