LRRC15 shows promise as a pediatric osteosarcoma immunotherapy target

Researchers are looking for more effective treatments for metastatic, relapsed or unresponsive pediatric osteosarcoma. One promising approach uses an immunotherapy called chimeric antigen receptor (CAR) T cells, which reprogram a patient’s immune cells to target a protein on cancer cells. However, the therapy needs to target a protein that maximizes tumor control while minimizing collateral toxicity to noncancer cells that also express that same protein. To find such targets, researchers at St. Jude previously performed a novel pan-cancer screen that found many potential candidates in solid tumors, including the protein LRRC15 for osteosarcoma. To further evaluate if LRRC15 was a good candidate target, scientists led by Christopher DeRenzo, MD, Department of Bone Marrow Transplantation & Cellular Therapy, tested CAR T cells targeting the protein using preclinical osteosarcoma models. Results showed LRRC15-CAR T cells had potent antitumor activity, leading to enhanced survival in multiple immunocompromised and immunocompetent osteosarcoma models while avoiding significant off-tumor toxicity. The findings, which were published in Clinical Cancer Research, suggest that researchers should further investigate LRRC15-CAR T–cell therapy for potential clinical use.

“Our work highlights the power of multidisciplinary collaboration to translate computational target discovery into therapeutic validation,” DeRenzo said. “It lays the foundation for more effective, precisely targeted CAR T–cell therapies for osteosarcoma and potentially other LRRC15-positive tumors.”

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