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

Translational Oncology (May 2020)

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

Affiliations

Meijun Zheng: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Lingyu Yu: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Juanjuan Hu: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Zongliang Zhang: State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Haiyang Wang: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Dan Lu: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Xin Tang: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Jianhan Huang: Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Kunhong Zhong: State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Zeng Wang: State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Yisong Li: Department of Laboratory Medicine, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Gang Guo: State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Shixi Liu: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China
Aiping Tong: State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China; Address all correspondence to: Hui Yang, Ph.D. or Aiping Tong, Ph.D. No. 37 Guo Xue Xiang Chengdu, 610041, P.R. China.
Hui Yang: Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, PR China; Address all correspondence to: Hui Yang, Ph.D. or Aiping Tong, Ph.D. No. 37 Guo Xue Xiang Chengdu, 610041, P.R. China.

Journal volume & issue: Vol. 13, no. 5

Abstract

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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.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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