Hyperactive Rac Dramatically Boosts CAR-M Therapeutic Efficacy
A New Challenge in Cancer Cell Targeting
Chimeric antigen receptor macrophages (CAR-M) represent an innovative immunotherapy that can engulf cancer cells, but in patients their bactericidal capacity has been limited. In particular, the tumor microenvironment often suppresses macrophage phagocytic activity.
Rac Hyperactivation Exponentially Enhances CAR-M
The research team introduced a gene that artificially hyperactivates the Rac protein into CAR-M. As a result, macrophages displayed markedly faster and stronger ingestion of cancer cells, more than doubling the baseline phagocytic efficiency.
Lethal "Trogosis": A Critical Survival Threshold
Rac hyperactivity converts the phenomenon termed "trogosis" into a lethal event. Previously, cancer cells could survive the subtle phagocytic process; now, hyperactive Rac drives immediate cell death during engulfment.
Future Implications
If translated to the clinic, this approach could provide a breakthrough for treating refractory and advanced tumors, offering patients a more effective form of immune‑based therapy.
Proceedings of the National Academy of Sciences, Volume 123, Issue 15, April 2026. Significance: Rac is a key protein in the cellular eating process called phagocytosis. Rac hyperactivity enhances the consumption of tumor cells by chimeric antigen receptor‑macrophages (CAR-M), a promising type of cellular immunotherapy. Elucidating the ...
In cancer treatment, the inability to achieve complete tumor eradication has been a major obstacle. By enabling more efficient removal of cancer cells, this strategy could allow patients to receive more potent immunotherapies and improve clinical outcomes.