Combination of Interleukin-11Rα chimeric antigen receptor T-cells and programmed death-1 blockade as an approach to targeting osteosarcoma cells In vitro

Abstract

Aim: To test whether combining interleukin (IL)-11Rα chimeric antigen receptor (CAR) T-cells with an anti-programmed death (PD-1) antibody (an immune checkpoint inhibitor) is an effective therapeutic approach in osteosarcoma (OS), allowing improved tumor eradication. Methods: IL-11Rα-CAR T-cells were cocultured in vitro with human LM7 OS tumor cells (with and without anti-PD-1 antibody). Coculture of LM7 cells with purified T-cells served as the control. Cytotoxicity and surface PD-1 expression were analyzed in all groups. Results: PD-1 expression increased during expansion of CAR T-cells. Exposure of immune cells to tumor cells in vitro subsequently decreased surface PD-1 expression on the CAR T-cells. Addition of an anti-PD-1 antibody (Clone J110) to further decrease surface PD-1 expression on CAR T-cells before coculture did not enhance cytotoxic effects of the CAR T-cells against LM7 cells. Conclusion: This combination of IL-11Rα-CAR T-cells and an anti-PD-1 antibody did not provide any additional cytotoxic benefit over IL-11Rα-CAR T-cell therapy alone in this setting. Further studies are needed as simple interference with surface PD-1 expression alone may not be sufficient to inhibit this immune checkpoint pathway to then enhance IL-11Rα-CAR T-cell therapeutic effects.