Researchers at Penn Medicine have developed an enhanced CAR T-cell therapy that achieves remission in over half of patients with resistant B-cell lymphomas, offering new hope where previous treatments have failed.
Key Points at a Glance
- New “armored” CAR T-cell therapy (huCART19-IL18) shows 81% tumor reduction and 52% complete remission in patients with relapsed/refractory B-cell lymphomas.
- Therapy incorporates interleukin 18 (IL18) to boost immune response and T-cell persistence.
- Shortened manufacturing process reduces CAR T-cell production time from 9–14 days to just 3 days.
- Study published in the New England Journal of Medicine; findings suggest potential applications beyond blood cancers.
Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of certain blood cancers by genetically modifying a patient’s own T cells to target and destroy malignant cells. However, many patients with B-cell lymphomas relapse or do not respond to existing CAR T-cell therapies, leaving them with limited options.
In a groundbreaking study led by researchers at the Perelman School of Medicine at the University of Pennsylvania, a next-generation CAR T-cell therapy, dubbed huCART19-IL18, has demonstrated remarkable efficacy in patients with relapsed or refractory B-cell lymphomas. This “armored” CAR T-cell therapy not only targets the CD19 antigen on B cells but also secretes interleukin 18 (IL18), a cytokine that enhances the immune response.
The phase I clinical trial included 21 patients who had undergone a median of seven prior treatments, including standard CAR T-cell therapies. Remarkably, 81% of these patients experienced tumor reduction, and 52% achieved complete remission. Some of the earliest patients treated have remained in remission for over two years.
Dr. Jakub Svoboda, associate professor of Hematology-Oncology and lead investigator of the trial, expressed optimism about the results: “I’m thrilled that this new generation of CAR T-cell therapy, created here at Penn, was highly effective in patients who have already tried everything available to treat their lymphoma.”
The addition of IL18 appears to play a crucial role in the therapy’s success. By secreting this cytokine, the modified T cells can recruit additional immune cells, bolster their own persistence, and overcome the immunosuppressive tumor microenvironment that often hinders treatment efficacy.
Importantly, the safety profile of huCART19-IL18 was consistent with existing CAR T-cell therapies. Patients experienced known side effects such as cytokine release syndrome (CRS) and neurotoxicity, which were managed successfully. No new or unexpected safety concerns were observed.
Another significant advancement is the streamlined manufacturing process for huCART19-IL18. Traditional CAR T-cell production can take 9 to 14 days, but the process developed by Penn’s Center for Cellular Immunotherapies reduces this to just three days. This acceleration is critical for patients with aggressive cancers who cannot afford delays in treatment.
Dr. Carl June, a pioneer in CAR T-cell therapy and senior author of the study, highlighted the broader implications of this approach: “Based on these results, we believe that incorporating cytokine secretion into CAR T-cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.”
The study’s findings, published in the New England Journal of Medicine, represent a significant step forward in cancer immunotherapy. By enhancing the functionality and persistence of CAR T cells, this innovative approach holds promise not only for patients with resistant B-cell lymphomas but potentially for those battling other challenging malignancies.
As research continues, the integration of cytokine-secreting capabilities into CAR T-cell therapies could redefine treatment paradigms and offer renewed hope to patients facing limited options.
