Bispecific T cell engagers and their synergistic tumor immunotherapy with oncolytic viruses

Qi Huang; Wen-Qi Cai; Zi-Wen Han; Mo-Yu Wang; Yang Zhou; Jun-Ting Cheng; Ying Zhang; Ying-Ying Wang; Qiang Xin; Xian-Wang Wang; Xiao-Chun Peng; Ying Xiang; Shu-Xian Fang; Zhao-Wu Ma; Hong-Yi Xin; Shu-Zhong Cui; Hong-Wu Xin

Bispecific T cell engagers and their synergistic tumor immunotherapy with oncolytic viruses

Am J Cancer Res. 2021 Jun 15;11(6):2430-2455. eCollection 2021.

Authors

Qi Huang^{1

2}, Wen-Qi Cai^{1

2}, Zi-Wen Han¹, Mo-Yu Wang^{1

2}, Yang Zhou^{1

2}, Jun-Ting Cheng^{1

2}, Ying Zhang³, Ying-Ying Wang^{1

2

4}, Qiang Xin⁵, Xian-Wang Wang^{1

6}, Xiao-Chun Peng^{1

7}, Ying Xiang^{1

2}, Shu-Xian Fang⁸, Zhao-Wu Ma^{1

2}, Hong-Yi Xin⁹, Shu-Zhong Cui⁸, Hong-Wu Xin^{1

2

10}

Affiliations

¹ Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University Jingzhou 434023, Hubei, China.
² Department of Biochemistry and Molecular Biology, School of Basic Medicine, Health Science Center, Yangtze University Jingzhou 434023, Hubei, China.
³ Department of Gastroenterology, Chun'an County First People's Hospital (Zhejiang Provincial People's Hospital Chun'an Branch) Hangzhou 311700, Zhejiang Province, China.
⁴ Department of Gynaecology, Comprehensive Cancer Center, Hannover Medical School D30625, Hannover, Germany.
⁵ Clinical Medicine Research Center, The Key Laboratory of Biological Cells of Inner Mongolia Autonomous Region, The Affiliated Hospital, Inner Mongolia Medical University Hohhot 010050, Inner Mongolia.
⁶ Department of Laboratory Medicine, School of Basic Medicine, Health Science Center, Yangtze University 1 Nanhuan Road, Jingzhou 434023, Hubei, China.
⁷ Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University Jingzhou 434023, Hubei, China.
⁸ Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University Guangzhou 510095, China.
⁹ Department of Microbiology and Immunology, Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Center for Life Sciences 28 Medical Drive, #03-09, 117456, Singapore.
¹⁰ Lianjiang People's Hospital Guangdong 524400, China.

PMID: 34249409
PMCID: PMC8263669

Abstract

Tumor immunotherapy, especially T cell based therapy, is becoming the main force in clinical tumor therapies. Bispecific T cell engager (BiTE) uses the single chain variable fragments (scFv) of two antibodies to redirect T cells to kill target cells. BiTEs for hematologic tumors has been approved for clinical use, and BiTEs for solid tumors showed therapeutic effects in clinical trials. Oncolytic viruses (OVs) of the adenovirus expressing p53 and herpes simplex virus expressing GM-CSF was approved for clinical use in 2003 and 2015, respectively, while other OVs showed therapeutic effects in clinical trials. However, BiTE and Oncolytic virus (OV) have their own limitations. We propose that OV-BiTE has a synergistic effect on tumor immunotherapy. Feng Yu et al. designed the first OV-BiTE in 2014, which remarkably eradicated tumors in mice. Here we review the latest development of the structure, function, preclinical studies and/or clinical trials of BiTE and OV-BiTE and provide perspective views for optimizing the design of OV-BiTE. There is no doubt that OV-BiTE is becoming an exciting new platform for tumor immunotherapy and will enter clinical trial soon. Exploring the therapeutic effects and safety of OV-BiTE for synergistic tumor immunotherapy will bring new hope to tumor patients.

Keywords: Bispecific T cell engager; immunotherapy; oncolytic virus; tumor.

Publication types

Review