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Journal of Immunology Research
Volume 2017, Article ID 6915912, 14 pages
https://doi.org/10.1155/2017/6915912
Research Article

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

1Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
2Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, China
3Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China

Correspondence should be addressed to Huizhong Li; nc.ude.umhzx@zhl and Junnian Zheng; nc.ude.umhzx@gnehznj

Received 7 August 2017; Revised 17 September 2017; Accepted 8 October 2017; Published 20 December 2017

Academic Editor: Rosa Molfetta

Copyright © 2017 Qing Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.