The development of CAR design for tumor CAR-T cell therapy

// Dandan Xu 1, * , Guoliang Jin 1, * , Dafei Chai 1 , Xiaowan Zhou 1 , Weiyu Gu 1 , Yanyun Chong 1 , Jingyuan Song 1 and Junnian Zheng 1, 2, 3 1 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China 2 Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China 3 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China * These authors contributed equally to this work Correspondence to: Jingyuan Song, email: songjy@xzhmu.edu.cn Junnian Zheng, email: jnzheng@xzhmu.edu.cn Keywords: CAR design; antigen target; co-stimulatory molecules; tumor microenvironment; safety Received: August 30, 2017 Accepted: December 04, 2017 Published: January 12, 2018 ABSTRACT In recent years, the chimeric antigen receptor modified T cells (Chimeric antigen receptor T cells, CAR-T) immunotherapy has developed rapidly, which has been considered the most promising therapy. Efforts to enhance the efficacy of CAR-based anti-tumor therapy have been made, such as the improvement of structures of CAR-T cells, including the development of extracellular antigen recognition receptors, intracellular co-stimulatory molecules and the combination application of CARs and synthetic small molecules. In addition, effects on the function of the CAR-T cells that the space distance between the antigen binding domains and tumor targets and the length of the spacer domains have are also being investigated. Given the fast-moving nature of this field, it is necessary to make a summary of the development of CAR-T cells. In this review, we mainly focus on the present design strategies of CAR-T cells with the hope that they can provide insights to increase the anti-tumor efficacy and safety.