Hu Juanjuan, Jiang Caiying, Zheng Meijun, Guo Yuxin, Tang Xin, Ren Jia, Lu Dan, Yu Lingyu, Gan Weigang, Liu Shixi, Tong Aiping, Yang Hui
Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University Chengdu, Sichuan, P. R. China.
State Key Laboratory of Biotherapy, West China Medical School, Sichuan University Chengdu, Sichuan, P. R. China.
Am J Transl Res. 2019 Aug 15;11(8):5183-5196. eCollection 2019.
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.
头颈癌（HNCs）是全球第六大常见癌症类型。尽管精细的手术技术和精确的靶向放疗有所发展，但HNC患者的预后仍然不佳。在此，我们研究了B7-H3在HNC中的表达谱，并验证B7-H3是否可通过抗B7-H3×CD3双特异性抗体（双抗）作为HNC的新型治疗靶点。我们分析了274例HNC样本中B7-H3的表达水平，并评估了B7-H3表达与临床病理参数之间的关联。构建了抗B7-H3×CD3双抗，并在体外和体内评估了这些双抗靶向HNC的疗效。结果显示，66.1%的临床HNC样本中检测到B7-H3高表达，且与较差的生存率相关。使用HNC细胞系在体外证实了抗B7-H3×CD3双抗的特异性抗肿瘤作用。在异种移植HNC小鼠模型中，抗B7-H3×CD3双抗延缓了肿瘤生长并延长了生存期。总之，B7-H3在HNC中经常过度表达，可能是双抗治疗的一个有前景的治疗靶点。
