Scientists have unveiled a “next generation” CAR-T therapy, aimed at treatment-resistant cancers.
Developers in Colorado, USA, say their “supercharged” version of CAR-T will enhance the effectiveness and longevity of the therapeutic cells. It is designed to be more sensitive than second-generation CAR-T therapy, able to attack leukaemia cells with low levels of antigens.
The new version of CAR-T is called ALA-CART, referring to the new adjunctive LAT-activating CAR-T cells. The researchers used human T cells and leukaemia cells in specialised mouse models and report that the novel ALA-CART cells show “promising” results against acute lymphocytic leukaemia (ALL) that was resistant to standard CAR-T treatment.
Researcher Dr Eric Kohler, of the University of Colorado Cancer Center, said CAR-T has had the same basic design for 15 years.
Dr Kohler said: “When we began this project, we wanted to understand why this design allowed certain leukaemia cells to escape therapy. Once we understood that, we knew how to design our ALA-CART cells. What was surprising is that we didn’t just fix the problem of leukaemia cells escaping, we improved multiple aspects of the ALA-CART cells, and we’re hopeful this will translate into improved outcomes for patients in the future.
“ALA-CART improves the ability of CAR-T cells to detect and attack resistant cancer cells more effectively. This could lead to longer lasting results, even when other treatments have failed. It also shows signs it could reduce side effects that often accompany traditional therapies.”
Fellow researcher Dr Catherine Danis said: “This marks a major shift in cancer immunotherapy, offering a ground-breaking innovation that could eventually improve survival and quality of life for patients with some of the most difficult-to-treat cancers.”
Source:
Pham-Danis C, Novak AJ, Danis E, McClellan SM, Leach L, Yarnell MC, Ebmeier CC, Tasian SK, Kohler ME. (2025) “Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia.” Cancer Cell, 10 March 2025, doi: 10.1016/j.ccell.2025.02.008.
Link: https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00060-1
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