新型双靶向全人源抗体在口腔鳞状细胞癌中的应用

A New Dual-targeting Full Human Antibody in Application of Oral Squamous Cell Carcinoma

目的发现并探讨新型抗HER3/EGFR双特异性抗体NB031在口腔鳞状细胞癌(OSCC)中的靶向治疗作用。方法筛选与鉴定双特异性抗体NB031;MTT法检测NB031对OSCC细胞增殖的影响;Western Blotting法检测NB031对下游信号通路的影响;通过建立裸鼠KB OSCC模型,比较生理盐水、cetuximab和NB031对肿瘤体积的影响。结果 Cetuximab和NB031均降低HSC3和KB细胞增殖能力,NB031抑制效果明显大于cetuximab;与cetuximab相比,NB031显著降低EGFR和HER3及它们下游信号的磷酸化;cetuximab和NB031均降低肿瘤体积增长速率,NB031作用更明显。结论相比cetuximab,NB031能够更有效地抑制人OSCC细胞生长,是一种具有潜在前景的靶向治疗制剂。

Objective To find and explore effect of a new bispecific antibody NB031 targeted both epidermal growth factor receptor （EGFR） and HER3 signaling in targeted therapy of oral squamous cell carcinoma （OSCC）. Meth-ods A bispecific antibody NB031 was screened and identified; MTT assay was performed to investigate the influence of NB031 on OSCC cell multiplication; the influence of NB031 on down-streamed signal pathway was identified using West-ern blot analysis; the effects of normal saline, Cetuximab and NB031 on tumor volumes were compared by establishing Xenotransplanted nude mouse tumorigenesis models of OSCC. Results Both Cetuximab and NB031 could inhibit cells proliferation of HSC3 and KB, and NB031 was more effective in inhibition than that by Cetuximab; compared with those by Cetuximab, NB031 significantly suppressed phosphorylation levels of EGFR, HER3 and both down-streamed signal;growth rate of tumor volume was decreased by both Cetuximab and NB031, and the inhibition effect of NB031 was more obvious than that of Cetuximab. Conclusion Compared with those by Cetuximab, NB031 may more effectively inhibit human OSCC cell growth, and it can be used as a potential prospect of agent for targeted therapy.