(1306-C) High-content immunofluorescence screen identifies ingenol-3-angelate to increase B7-H3-CAR T antigen expression on lung metastatic osteosarcoma cells
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: CAR T cell therapy offers a potential strategy to improve the efficacy and reduce the toxicity of the treatment for cancer patients. However, current CAR T cell therapy has difficulties in effectively treating solid tumors. To overcome the challenges, various approaches such as combinational treatment have been investigated. Our goal is to identify compounds that increase the expression of B7-H3, a protein on the surface of metastatic osteosarcoma cells that is targeted by B7-H3-CAR T cells. This would improve the efficacy of B7-H3-CAR T cell therapy against cancer cells. To achieve this goal, we developed an immunofluorescence-based high-content screen that measures the endogenous cell surface expression levels of B7-H3 protein. Screening 1114 FDA-approved drugs identified that ingenol-3-angelate increased B7-H3 protein expression. Further validation found that ingenol-3-angelate increased B7-H3 total and cell surface protein expression via protein kinase C alpha. In addition, ingenol-3-angelate enhanced B7-H3 CAR T cell function to kill LM7 osteosarcoma cells. This proof-of-principle screen demonstrates that identifying compounds that increase the cell surface expression of B7-H3 on cancer cells could improve the B7-H3-CAR T cell function.