Anti-CD40 mAb enhanced efficacy of anti-PD1 against osteosarcoma

In this study, we established the osteosarcoma mouse tumor model resistant to anti-PD1 mAb that harbored PD1hi T cells. Furthermore, flow cytometry analysis of tumor infiltrating leukocytes after treatment was used as a screening platform to identify agents that could re-sensitize T cells to anti-PD1 mAb. Results showed that anti-CD40 mAb treatment converted PD1hi T cells to PD1lo T cells, reversing phenotypic T cell exhaustion and sensitizing anti-PD1 refractory tumors to respond to anti-PD1 mAb. Results also showed that intratumor Treg presented with a less activated and attenuated suppressive phenotype after anti-CD40 mAb treatment. Our study provides proof of concept to systematically identify immune conditioning agents, which are able to convert PD1hi T cells to PD1lo T cells, with clinical implications in the treatment against refractory osteosarcoma to anti-PD1 mAb.
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research