Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma.

Abstract	The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK) therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR-) specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92) against renal cell carcinoma (RCC) cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.
Authors	Qing Zhang, Kang Tian, Jinjing Xu, Haixu Zhang, Liantao Li, Qiang Fu, Dafei Chai, Huizhong Li, Junnian Zheng
Journal	Journal of immunology research (J Immunol Res) Vol. 2017 Pg. 6915912 ( 2017) ISSN: 2314-7156 [Electronic] Egypt
PMID	29423418 (Publication Type: Journal Article)
Chemical References	Anilides Antineoplastic Agents Pyridines Receptors, Antigen Recombinant Fusion Proteins cabozantinib EGFR protein, human ErbB Receptors
Topics	Anilides (therapeutic use) Animals Antineoplastic Agents (therapeutic use) Carcinoma, Renal Cell (drug therapy) Cell Line Combined Modality Therapy Cytotoxicity, Immunologic ErbB Receptors (immunology) Female Humans Immunotherapy, Adoptive (methods) Kidney Neoplasms (drug therapy) Killer Cells, Natural (immunology, transplantation) Mice Mice, SCID Pyridines (therapeutic use) Receptors, Antigen (genetics) Recombinant Fusion Proteins (genetics) Xenograft Model Antitumor Assays

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