Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma

Meijun Zheng; Lingyu Yu; Juanjuan Hu; Zongliang Zhang; Haiyang Wang; Dan Lu; Xin Tang; Jianhan Huang; Kunhong Zhong; Zeng Wang; Yisong Li; Gang Guo; Shixi Liu; Aiping Tong; Hui Yang

doi:10.1016/j.tranon.2020.100770

Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma

Transl Oncol. 2020 May;13(5):100770. doi: 10.1016/j.tranon.2020.100770. Epub 2020 Apr 13.

Authors

Meijun Zheng¹, Lingyu Yu¹, Juanjuan Hu¹, Zongliang Zhang², Haiyang Wang¹, Dan Lu¹, Xin Tang³, Jianhan Huang³, Kunhong Zhong², Zeng Wang², Yisong Li⁴, Gang Guo², Shixi Liu¹, Aiping Tong⁵, Hui Yang⁶

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China.
² State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China.
³ Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China.
⁴ Department of Laboratory Medicine, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China.
⁵ State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China. Electronic address: aipingtong@scu.edu.cn.
⁶ Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China. Electronic address: yh8806@163.com.

Abstract

Extranodal nasal natural killer (NK)/T cell lymphoma (ENKTCL) is a rare but highly aggressive subtype of non-Hodgkin lymphoma (NHL). Nevertheless, despite extensive research, the estimated 5-year overall survival of affected patients remains low. Therefore, new treatment strategies are needed urgently. Recent advances in immunotherapy have the potential to broaden the applications of chimeric antigen receptor-modified T (CAR-T) cells and the bispecific T-cell engaging (BiTE) antibody. Here, we screened a panel of biomarkers including the B7-H3, CD70, TIM-3, VISTA, ICAM-1, and PD-1 in NKTCL cell lines. As a result, we found for the first time that B7-H3 was highly and homogeneously expressed in these cells. Consequently, we constructed a novel anti-B7-H3/CD3 BiTE antibody and B7-H3-redirected CAR-T cells, and evaluated their efficacy against NKTCL cel lines both in vitro and in vivo. Notably, we found that both anti-B7-H3/CD3 BiTE and B7-H3-redirected CAR-T cells effectively targeted and killed NKTCL cells in vitro, and suppressed the growth of NKTCL tumors in NSG mouse models. Thus, B7-H3 might be a promising therapeutic target for treating patients with NKTCL tumors.