Using CD5 KO to boost the clinical efficacy of adoptive T-cell immunotherapy
Patel RP, Ghilardi G, Zhang Y, et al. CD5 Deletion Enhances the Antitumor Activity of Adoptive T Cell Therapies. Science Immunology. 2024; 9 (97) (doi: 10.1126/sciimmunol.adn6509).
With evidence showing that the scavenger receptor CD5 inhibits chimeric antigen receptor (CAR) T-cell activation, investigators believe that CD5 knockout is the key to improving the clinical efficacy of adoptive T-cell immunotherapy. The success of such interventions is currently undermined by CAR T cell dysfunction or failure of T cells to expand and/or persist following CAR infusion. To avoid interference with T cell function by CD5, investigators used CRISPR-Cas9 to block the receptor. CD5 deletion, according to the research, ramps up T-cell effector function through increased cytotoxicity, in vivo expansion, and persistence. Importantly, the enhanced anti-tumor behavior — demonstrated in multiple hematological and solid cancer models — does not appear to have toxic effects.