New clinical trials from University Hospitals

CLEVELAND – Newly designed chimeric antigen receptor (CAR) T cells targeting CD19 antigen are effective in the treatment of adults and children with B-cell malignancies, particularly when produced as part of the On-site fabrication, available at Seidman Cancer Center teaching hospitals (UH). This is the conclusion of a recent study published in the prestigious journal Nature Communication, detailing two phase I clinical trials of CAR19 T cells used to treat patients with relapsed / refractory pediatric acute lymphocytic B-cell leukemia (ALL) or adult B-cell lymphoma.

“Point-of-care manufacturing can improve performance and accessibility by avoiding the need to cryopreserve and transport cells to centralized facilities,” says Jane Reese Koc, study co-author, COO of cell therapy at the UH Seidman Cancer Center and the National Center for Regenerative. Medicine at Case Western Reserve University. The cell therapy lab is shared by the National Center for Regenerative Medicine, the Case Comprehensive Cancer Center, and the UH Seidman Cancer Center. “The results of this study confirm the safety and efficacy of this approach. “

“One of the main advantages of this approach is the ability to treat patients much faster than with commercial CAR T products,” adds study co-author David Wald, MD, PhD, associate director of the basic research at the Wesley Center for Immunotherapy. at UH Seidman Cancer Center and Associate Professor of Pathology Case Western Reserve University School of Medicine. “Commercial products can take three to six weeks to manufacture. Saving time for treatment with the method is important for those patients who have advanced malignant tumors. We are working with partners to develop even faster methods to reduce the manufacturing method to a single day.

The phase I trials involved 31 pediatric patients and 23 adult patients, located in both Russia and Cleveland. After a median follow-up of 17 months, the one-year survival rate for ALL complete responders was 79.2% and the median duration of response was 10.2 months. For non-Hodgkin lymphoma (NHL), the one-year survival of complete responders was 92.9% and the median duration of response was not reached. CAR19 T cells were first tested in cancer cell lines and mouse xenograft models, with positive results.

“For NHL, the results have been excellent,” says hematologist Leland Metheny, MD, who is also involved in these clinical trials at the UH Seidman Cancer Center. “The results showed that they were largely curative.”

Importantly, in mouse xenograft experiments, fresh CAR19 T cells produced in the local facility were shown to provide an advantage over cryopreserved cells more commonly used in CAR T applications. of fresh CAR19 T cells resulted in a significantly lower tumor burden compared to frozen CAR19 T cells at equivalent dose on days 11 and 13 of the study. groups treated. However, the fresh cells reduced the tumor burden earlier than eight days and immediately began to reduce the tumor burden, while the frozen CAR19 T cells first allowed tumor growth before controlling the growth.

“Cells that were fresh worked much better and more efficiently in mice to get rid of NHL than cells that were frozen,” says Dr. Metheny. “There is something we do not yet know about the impact of the freezing technique that affects CAR T cells.”

In addition to these two clinical trials, Dr. Metheny’s colleagues at the UH Seidman Cancer Center are also conducting a CAR T trial that uses all-human proteins – just a handful of sites nationwide to offer this option to patients. .

“The antibody part of the antigen receptor that we place on the surface of the T cell is an entirely human sequence,” says UH oncologist Seidman Benjamin Tomlinson, MD, who is leading the assay. “In theory, there may be fewer unwanted events, so be slightly safer, while still attacking the same target. The bigger question is whether, by not having a foreign component, it can be a little more effective in instigating signaling. Human to human should connect a little better than human to mouse, and this may not generate the kind of reactions we’re used to seeing with a regular CAR T. So that’s what we’re exploring. We have opened this humanized CAR T trial and have successfully treated patients with lymphoma and ALL.

In addition, Dr. Wald and colleagues recently reported at the American Society of Hematology meeting on their work identifying potential biomarkers that may help predict outcomes for patients receiving CAR T cell therapy. .

“We hope this will help design next-generation CAR T cell therapies,” he says.

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About Seidman Cancer Center Teaching Hospitals

The UH Seidman Cancer Center is the only stand-alone cancer hospital in Northeast Ohio, where all clinicians and staff are dedicated to the prevention, diagnosis and treatment of cancer while researching innovative new treatment options. through clinical trials. Nationally classified cancer care is also available for patients in the 11 county area at 18 community sites. Our specialists at UH Seidman form 14 specialist cancer teams and focus on determining integrated care plans tailored to patient needs. The UH Seidman Cancer Center is part of the Case Comprehensive Cancer Center at Case Western Reserve University, one of the 51 comprehensive cancer centers nationwide, designated by the National Cancer Institute (NCI). Patients have access to advanced treatment options, ranging from a pioneering stem cell transplant program founded over 40 years ago and a wide range of immunotherapies at the first and only proton therapy center in the north of the ‘Ohio for adults and children. Go to UHhospitals.org/Seidman for more information.

About University Hospitals / Cleveland, Ohio
Founded in 1866, University Hospitals serve the needs of patients through an integrated network of 23 hospitals (including 5 joint ventures), more than 50 health centers and ambulatory care facilities, and more than 200 physician offices in 16 northern counties from Ohio. The system’s flagship quaternary care academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, the University of Oxford, and the Technion Israel Institute of Technology. The main campus also includes the UH Rainbow Babies & Children’s Hospital, ranked among the top children’s hospitals in the country; UH MacDonald Women’s Hospital, Ohio’s only women’s hospital; and UH Seidman Cancer Center, which is part of the NCI-designated Case Comprehensive Cancer Center. The UH is home to some of the country’s most prestigious clinical and research programs, with more than 3,000 clinical trials and research studies underway. UH Cleveland Medical Center consistently ranks among the top performers in nationwide ranking polls, including US News & World Report’s “Best Hospitals in America”. The UH is also home to 19 research and clinical care institutes. UH is one of Northeast Ohio’s largest employers with over 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information visit UHhospitals.org.


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