Advanced Genetic Screening May Improve CAR-T Cell Therapy for Multiple Myeloma and Other Cancers

Researchers from Mass General Brigham and the Broad Institute of MIT and Harvard have made a significant breakthrough in cancer immunotherapy by identifying genetic modifications that could enhance the effectiveness of chimeric antigen receptor (CAR)-T cell therapy. This innovative approach involves using CRISPR screening technology to discover genes that influence T cell performance and longevity, both in laboratory cultures and in preclinical models of multiple myeloma.

The study, published in the journal Nature, demonstrates that manipulating specific genes can boost CAR-T cell persistence and anti-tumor activity. Notably, the deletion of the gene CDKN1B, a regulator of the cell cycle, was shown to significantly increase CAR-T cell proliferation and their ability to combat tumors over an extended period.

The scientists conducted comprehensive in vitro experiments and further validated their findings in mouse models, tracking the modified CAR-T cells for up to 21 days. They observed that certain genetic alterations improved both early activation and long-term sustainability of the therapy, which are critical factors for successful treatment.

This research presents a promising pathway toward more effective CAR-T therapies, particularly for hard-to-treat cancers such as solid tumors and relapsed or refractory multiple myeloma, where current treatments have limited success. The ability to rapidly test multiple genetic modifications could accelerate the development of tailored immunotherapies, offering hope for patients with challenging cancers.

According to co-senior author Dr. Robert Manguso, the in vivo screening approach revealed regulators that traditional in vitro studies could not predict, emphasizing the importance of testing in living systems. Dr. Marcela Maus highlighted the efficiency of this high-throughput method, which can identify potential therapeutic targets more quickly and cost-effectively than traditional methods.

Overall, this pioneering work suggests that targeted genetic modifications in CAR-T cells, like the suppression of CDKN1B, can enhance treatment outcomes, paving the way for next-generation cancer immunotherapies.