点突变
突变
抗体
抗性(生态学)
生物
遗传学
计算生物学
基因
生态学
作者
Xinlei Zhuang,Shuqing Chen,Liqiang Pan
出处
期刊:Methods in molecular biology
日期:2024-01-01
卷期号:: 41-54
标识
DOI:10.1007/978-1-0716-3798-2_3
摘要
Resistance to therapeutic antibodies caused by on-target point mutations is a major obstacle in anticancer therapy, creating an "unmet clinical need." To tackle this problem, researchers are developing new generations of antibody drugs that can overcome the resistance mechanisms of existing agents. We have previously reported a structure-guided and phage-assisted evolution (SGAPAE) approach to evolve cetuximab, a therapeutic antibody, to effectively reverse the resistance driven by EGFRS492R or EGFRG465R mutations, without changing the binding epitope or compromising the antibody efficacy. In this protocol, we provide detailed instructions on how to use the SGAPAE approach to evolve cetuximab, which can also be applied to other therapeutic antibodies for reversing on-target point mutation-mediated resistance. The protocol consists of four steps: structure preparation, computational prediction, phage display library construction, and antibody candidate selection.
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