New ‘armored’ CAR produces responses in patients whose cancer does not respond to current CAR T-cell therapies

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Although CAR T-cell therapy has revolutionized the treatment of many blood cancers, including non-Hodgkin’s lymphoma (NHL), many patients who receive CAR T-cell therapy do not experience long-term remission. For those whose cancer returns or becomes resistant after CAR T-cell therapy, the prognosis is poor and few options remain.

A new “armored” form of CAR T-cell therapy, developed by Carl June, MD, the Richard W. Vage Professor of Immunotherapy at the University of Pennsylvania Perelman School of Medicine, may help these patients.

According to the results of a phase I clinical trial, presented today at the Annual Meeting of the American Society of Clinical Oncology (ASCO). (Summary 7004), the new CAR T was safe and had a three-month overall response rate of 80% in 20 patients with NHL whose cancer came back or stopped responding to treatment after receiving a commercially available CAR T-cell therapy.

“By the time we treat someone with commercially available, FDA-approved CAR T cell therapies, they have already tried at least one other treatment that either didn’t work at all or their lymphoma relapsed, and they are very hopeful that CAR T cell therapy – which has made such a difference for so many – will work for them too,” said Jakub Svoboda, MD, associate professor of Hematology-Oncology, who led the clinical trial at Penn Medicine’s Abramson Cancer Center.

“If the standard of care CAR T-cell therapy does not work for them, it is incredibly disappointing. While we still have more follow-up to do, it is gratifying to see so many patients with lymphoma responding to this newly developed CAR T-cell product. here at Penn.”

The first-in-human study evaluated huCART19-IL18, an anti-CD19 CAR that was further modified to secrete the pro-inflammatory cytokine, interleukin 18 (IL 18), based on preclinical studies showing that it reduces CAR T activity could improve.

“We compared this CAR T to an armored truck or tank, because the release of IL 18 further protects the CAR T cells and promotes their ability to attack the cancer cells,” said June, whose groundbreaking research led to the first approved CAR T. cell therapy in 2017.

The production of huCART19-IL18 also uses a process developed by Penn’s Center for Cellular Immunotherapies that shortens the production time of the CAR T cells to three days. For patients with aggressive, fast-growing cancers, this means they can begin CAR T-cell therapy sooner than is currently possible with standard turnaround times of nine to 14 days. a earlier, preclinical research had discovered that the shortened production time can also increase the potency of the T cells.

The addition of IL 18 resulted in no new or unexpected safety concerns, apart from the known side effects of CAR T cell therapy, including cytokine release syndrome (CRS) and neurotoxicity, which were successfully managed. As patient follow-up continues, median overall survival after treatment has not yet been determined, with some of the earliest patients now being treated now in remission for two years or more. These results represent an update of early data presented at the 2022 American Society of Hematology (ASH) annual meeting.

Svoboda will present the research during an oral abstract session on Saturday, June 1 at 3:00 PM CT in S100bc.

Provided by Perelman School of Medicine at the University of Pennsylvania


Abstract: Jakub Svoboda et al., Safety and efficacy of armored huCART19-IL18 in patients with relapsed/refractory lymphomas that progressed after anti-CD19 CAR T cells

Quote: New ‘armored’ CAR produces responses in patients whose cancer does not respond to current CAR T-cell therapies (2024, June 1) retrieved June 1, 2024 from https://medicalxpress.com/news/2024-05-armored -car -reactions-patients-cancers.html

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