Overexpression of B7-H3 as an opportunity for targeted therapy in head and neck cancers

Juanjuan Hu; Caiying Jiang; Meijun Zheng; Yuxin Guo; Xin Tang; Jia Ren; Dan Lu; Lingyu Yu; Weigang Gan; Shixi Liu; Aiping Tong; Hui Yang

Overexpression of B7-H3 as an opportunity for targeted therapy in head and neck cancers

Am J Transl Res. 2019 Aug 15;11(8):5183-5196. eCollection 2019.

Authors

Juanjuan Hu¹, Caiying Jiang², Meijun Zheng¹, Yuxin Guo³, Xin Tang⁴, Jia Ren¹, Dan Lu¹, Lingyu Yu¹, Weigang Gan^{1

5}, Shixi Liu¹, Aiping Tong², Hui Yang¹

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University Chengdu, Sichuan, P. R. China.
² State Key Laboratory of Biotherapy, West China Medical School, Sichuan University Chengdu, Sichuan, P. R. China.
³ Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University Chengdu, Sichuan, P. R. China.
⁴ West China Medical School, Sichuan University Chengdu, Sichuan, P. R. China.
⁵ Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of North Sichuan Medical College Nanchong, Sichuan, P. R. China.

PMID: 31497233
PMCID: PMC6731436

Abstract

Head and neck cancers (HNCs) are the sixth most common type of cancer in the world. Despite the development of refined surgical techniques and precise targeted radiation, patients with HNCs have a dismal prognosis. Here, we examine the expression profile of B7-H3 in HNCs and verify whether B7-H3 can serve as a novel therapeutic target for HNCs via anti-B7-H3×CD3 bispecific antibodies (biAbs). We analyzed the expression level of B7-H3 in 274 HNC samples and evaluated the association between B7-H3 expression and clinicopathological parameters. Anti-B7-H3×CD3 biAbs were constructed, and the efficacy of these biAbs in targeting HNCs was assessed in vitro and in vivo. As a result, high expression of B7-H3 was detected in 66.1% of clinical HNC samples and was correlated with poor survival. Specific antitumor effects of anti-B7-H3×CD3 biAbs were confirmed in vitro using HNC cell lines. In xenograft HNC mouse model, anti-B7-H3×CD3 biAbs delayed tumor growth and prolonged survival. In conclusion, B7-H3 is frequently overexpressed in HNCs and could be a promising therapeutic target for biAb therapy.

Keywords: B7-H3; bispecific antibodies; head and neck cancers; immunotherapy.