Combination Therapy with EGFR Specific CAR_NK_92 Cells and Cabozantinib against Human Renal Cell Carcinoma

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Youqing Huang, Yong Zhong, Chunhui Qin, Hao Wang

Abstract

Adaptive therapy using immune effector cells engineered by means of chimeric antigen receptors (CAR) has risen as a hopeful cancer management option. Despite their unprecedented success in haematological malignancies, CAR-modified T cells have shown limited efficacy in solid tumours, as the tumor's immune-suppressive microenvironment inhibits CAR-modified immune effector cells' functionality by different pathways, counting checkpoint receptor ligands expression like PD-L1 & recruitment tregs like suppressive immune cells. Receptor of epidermal growth factor (EGFR) could be the target of a II-generation Chimeric antigen receptor T cellshat was transduced to NK-92 cell. In our research, we examined the antitumor efficacy of EGFR specific NK-92 (CAR-NK-92) cells using a xenograft mice model & in conjunction with tyrosine kinase inhibitor cabozantinib. We discovered that EGFR positive renal carcinoma cells (RCC) 786-O and ACHN may specifically detect and activate CAR_NK_92 cells. They also displayed particular cytotoxicity against RCC in in vitro & in vivo models. Furthermore, we discovered that cabozantinib improves RCC-specific cytotoxicity by enhancing the expression of EGFR while reducing PD-L1 expression in RCC. Our research shows that CAR_NK_92 cells possess anti cancer therapeutic potential for EGFR-positive tumour cells, and that cabozantinib can boost CAR_NK_92 cell cytotoxicity when treated together.

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