LRRC15 as a target for CAR T therapy in osteosarcoma
O'Reilly C, Tuladhar S, Nguyen P, et al. LRRC15-CAR T Cells for the Treatment of Osteosarcoma. Clinical Cancer Research. 2026; (doi: 10.1158/1078-0432.CCR-24-2335).
Early research suggests leucine rich repeat containing 15 (LRRC15), which is highly present in osteosarcoma tumors but limited in normal tissues, has potential as a target antigen for chimeric antigen receptor (CAR) T cell therapy. Investigators engineered LRRC15-CAR T cells and applied preclinical models to assess safety and anti-tumor effect against osteosarcoma. The findings were favorable, with the cells showing specificity and cytotoxicity against LRRC15-positive targets in vitro. They demonstrated anti-tumor activity — and, subsequently, greatly improved survival compared with controls — in vivo in human xenograft and immunocompetent mouse models. The combination of anti-osteosarcoma activity and a favorable safety profile make a strong argument for clinical translation of LRRC15-CAR T cells in patients with osteosarcoma and possibly other LRRC15-expressing solid tumors, the researchers conclude.