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Qing Zhang [1] and Kang Tian [1] and Jinjing Xu [1] and Haixu Zhang [1] and Liantao Li [1] and Qiang Fu [2] and Dafei Chai [1] and Huizhong Li [1] and Junnian Zheng [1; 3]

Academic Editor: Rosa Molfetta

1, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China, xzmc.edu.cn

2, Department of Immunology, Binzhou Medical University, Yantai, Shandong 264003, China, bzmc.edu.cn

3, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China, xzmc.edu.cn

Received Aug 7, 2017; Revised Sep 17, 2017; Accepted Oct 8, 2017

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.

1. Introduction

Renal cell carcinoma (RCC) remains one of the most lethal urological cancers. Metastasis and recurrence occur in 20–30% of patients that received radical resection. It is also not sensitive to conventional radiotherapy and chemotherapy [1]. In recent years, small-molecule targeted therapy, including tyrosine kinase inhibitors (TKI), became the first-line treatment for metastatic RCC, though prognosis remains poor [2]. Immunotherapy is an exciting treatment option for RCC in the past decade. The most common immunotherapy includes cytokine therapy and immune checkpoint inhibition [3]. The use of cytokine therapy such as IL-2 and IFN-α declined because of modest response rates and poor tolerability. Immune checkpoint inhibitors have made significant progress and gained much attention with their approval for use in various solid tumors including RCC. However, their objective response rates are only 15–35% [4]. Therefore, it is urgent to develop new strategies to treat RCC.

The chimeric antigen receptor-modified T cell (CAR-T) therapy is a newly developed adoptive treatment of cancer. CAR-T therapy has achieved a gratifying breakthrough in hematological malignancies and showed exciting efficacy in some solid tumors, such as metastatic neuroblastoma [5, 6], recurrent glioblastoma [7], and prostate cancer [8]. However, its therapeutic efficacy in other solid tumors including RCC is less impressive. Lamers et al. designed a first-generation CAR (scFv-FcRγ) directed against carboxy anhydrase IX (CAIX) and used the CAR-modified T cells to treat patients with CAIX-expressing metastatic RCC [9]. Although blood cytokine profiles mirrored CAR-T cell presence and in vivo activity,...

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