Driving better and safer HER2-specific CARs for cancer therapy

// Xianqiang Liu 1, * , Nan Zhang 2, * and Huan Shi 3 1 Department of Breast and Thyroid Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China 2 Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China 3 Department of Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China * These authors contributed equally to this work Correspondence to: Huan Shi, email: huanshidoc@gmail.com Keywords: chimeric antigen receptor, HER2, cancer, immunotherapy, toxicity Received: March 20, 2017      Accepted: April 14, 2017      Published: April 29, 2017 ABSTRACT Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from “on-target, off-tumor” recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity. Furthermore, we also discuss the main strategies for improving the safety of HER2 CAR-based cancer therapies.