Modified car-t for a reinforced response
CAR-T Cells, or T lymphocytes with chimerical antigenic receptor, stand out as a key immunotherapy approach for certain blood cancers, including B lymphomas and acute leukemia. In France, around 2,000 patients could benefit from it each year, mainly after failure of several conventional treatments. Although personalized and promising, these treatments are still hampered by their cost and significant logistical constraints.
However, their effectiveness remains incomplete: more than half of the treated patients relapse or develop resistance. To answer this problem, a team from the University of Pennsylvania, led by Dr. Jakub Svoboda, tested an improved version, called “Army”, named huCART19-IL18. This new generation of CAR-T targets always the CD19 antigen but is designed to secreteInterleukin-18 (IL-18)a pro-inflammatory cytokine intended to strengthen the immune response and the sustainability of modified cells.
Promising results despite the history of failure
Phase I study, published in May 2025 in the New England Journal of Medicineincluded 21 patients in the therapeutic failure, with a median of seven previous treatments. Despite this difficult context, 81 % presented a partial or complete response three months after the infusion, including 52 % full responses. Some patients have maintained their remission beyond two years.
The undesirable effects remained within the expected limits: 62 % presented cytokine (mainly moderate) and 14 % A light neurotoxicity. No unexpected side effects have been reported.
The treatment has another major asset: its manufacture in three days, against 9 to 14 days usually. This reduced time makes it possible to preserve less differentiated T cells, often more effective and persistent.
The clinician’s point of view
Dr. Jérôme Barrière, medical oncologist, praised the interest of this advance on social networks:
-“CAR-T cell treatment is a full-development cell immunotherapy strategy, which aims to fight cancer based on the patient’s own immune system. »»
“In this study, an improved version, Hucart19-Il18, was tested after failure of a first CAR treatment. These cells are said to be armed, because they secrete interleukin-18 to strengthen the antitumoral effect. »»
“The results are very encouraging: 81 % response, including 52 % full. And this, with moderate toxicity, even at low doses. »»
“The more we advance, the more we manage to understand why certain treatments do not work and how to try to bypass the resistance mechanism. »»
Towards a new generation of cell therapies
This advance could pave the way for new indications. The researchers are already planning to extend Hucart19-Il18 to acute and chronic leukemia, and other forms of lymphomas. In addition, the technological platform developed for this therapy could be used in other projects, thanks to current industrial partnerships.
According to Carl June, pioneer of CAR-T and director of the Center for Cellular Immunotherapies at the University of Pennsylvania, this approach enriched in cytokines could also apply to solid tumors, so far not very sensitive to cell therapies. The IL-18, produced locally, would stimulate immunity without generating systemic toxicity.
Source : New England Journal of MedicineMay 7, 2025; EurekAlert!press release from May 7, 2025.
DOI
10.1056/Nejmoa2408771
