An “armoured” version of CAR-T treatment has shown promise against treatment-resistant B-cell lymphoma, researchers have reported.
More than half of the 21 patients in a phase I trial experienced complete remissions, the researchers at the University of Pennsylvania, USA, have reported.
The enhanced treatment, known as huCART19-IL18, secretes interleukin 18, which the researchers say enhances the immune system and provides additional protection to CAR-T cells. It is the first time a cytokine-enhanced CAR-T treatment has been tested on blood cancer patients.
The findings were reported in the New England Journal of Medicine last week.
The 21 patients in the trial had received on average seven other therapies each for B-cell lymphoma – and all but one had tried an existing CAR-T therapy. According to the findings, the new treatment reduced the cancer in 17 patients (81%) and led to complete remission in 11 patients (52%).
Lead author of the study Dr Jakub Svoboda from University of Pennsylvania said: “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.
“It’s also encouraging to see that the toxicity of this novel product was not different than what we already see with commercial CARs.”
Study leader Professor Carl June said: “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. With longer T cell persistence and expansion, this strategy could be powerful in settings where CAR-T hasn’t performed as well, such as solid tumours.”
The developers are now hoping to extend the trials to patients with acute lymphoblastic leukaemia and chronic lymphocytic leukaemia.
Source:
Svoboda J, Landsburg DJ, Gerson J, Nasta SD, Barta SK, Chong EA, Cook M, Frey NV, Shea J, Cervini A, Marshall A, Four M, Davis MM, Jadlowsky JK, Chew A, Pequignot E, Gonzalez V, Noll JH, Paruzzo L, Rojas-Levine J, Plesa G, Scholler J, Siegel DL, Levine BL, Porter DL, Ghassemi S, Ruella M, Rech A, Leskowitz RM, Fraietta JA, Hwang WT, Hexner E, Schuster SJ, June CH. (2025) “Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure.” New England Journal of Medicine, 8 May 2025, doi: 10.1056/NEJMoa2408771.
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2408771
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