Department of Medical Biotechnology, School of Medical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Mol Biotechnol. 2021 Jun;63(6):525-533. doi: 10.1007/s12033-021-00317-8. Epub 2021 Mar 26.
Targeted therapy is an effective and appropriate approach with low side effects in cancer therapy compared with other treatment approaches. Epidermal growth factor receptor, EGFR, is a favorable biomarker as targeted therapy because it overexpresses in several cancers. Monoclonal antibodies are common agents for targeted therapy. Nanobody is the smallest format of monoclonal antibodies with unique properties that include hiding epitope targeting, high stability, low production cost, and ease of connection to other components. The main challenge in targeted therapy by monoclonal antibodies is their immunogenicity due to their non-human nature. In this study, we designed, constructed, and evaluated a novel humanized anti- EGFR biparatopic nanobody, hu7CG2. The hu7CG2 was designed by grafting the complementarity-determining regions of two camelid anti- EGFR nanobodies known as 7C12 and EG2 to a universal scaffold and then connected with a glycine-serine linker. The results of antigen-binding activity and cell viability assays showed that the hu7CG2 inhibited the growth of EGFR overexpression tumor cells. The data showed that hu7CG2 might be a useful tool in the targeting and treatment of tumor cells.
与其他治疗方法相比，靶向治疗在癌症治疗中具有副作用低、疗效确切的特点。表皮生长因子受体（EGFR）是一种有前途的靶向治疗生物标志物，因为它在多种癌症中过度表达。单克隆抗体是靶向治疗的常用药物。纳米抗体是单克隆抗体的最小形式，具有独特的性质，包括隐藏表位靶向、高稳定性、低成本和易于与其他成分连接。单克隆抗体靶向治疗的主要挑战是其免疫原性，因为它们是非人类的。在这项研究中，我们设计、构建和评估了一种新型的人源化抗 EGFR 双价纳米抗体 hu7CG2。hu7CG2 通过将两种骆驼源抗 EGFR 纳米抗体 7C12 和 EG2 的互补决定区移植到一个通用支架上，并通过甘氨酸-丝氨酸接头连接而设计。抗原结合活性和细胞活力测定结果表明，hu7CG2 抑制了 EGFR 过表达肿瘤细胞的生长。数据表明，hu7CG2 可能是肿瘤细胞靶向治疗的有用工具。
