Centre for Tumour Biology, Barts Cancer Institute-Cancer Research UK Centre of Excellence, Queen Mary University of London, Charterhouse Square London, UK.
Expert Opin Drug Discov. 2021 Jul;16(7):737-744. doi: 10.1080/17460441.2021.1878143. Epub 2021 Feb 3.
: The integrin αvβ6 is a promising therapeutic target due to its limited expression in healthy tissue and significant overexpression in cancer and fibrosis. The peptide A20FMDV2, derived from the foot and mouth disease virus, is highly selective for αvβ6, and can be used therapeutically to target αvβ6 expressing cells.: In this review, the authors discuss the logic that led to the discovery of A20FMDV2, the importance of its stereochemistry in receptor-binding, and the strategies employed to use it as a molecular-specific drug delivery system. These strategies include creating A20FMDV2-drug conjugates, genetically modifying oncolytic viruses to express A20FMDV2 and thus redirect their tropism to predominantly αvβ6 expressing cells, creation of A20FMDV2 expressing CAR T-cells, and modifying antibody tropism by inserting A20FMDV2 into the CDR3 loop.: αvβ6 is one of the most promising therapeutic targets in cancer and fibrosis discovered in the last few decades. The potential use of A20FMDV2 as a molecular-specific αvβ6-targeting agent is extremely promising, particularly when considering the success of the peptide and its variants in clinical imaging.
整合素 αvβ6 在健康组织中的表达有限,而在癌症和纤维化中过度表达,因此成为有前途的治疗靶点。源自口蹄疫病毒的肽 A20FMDV2 对 αvβ6 具有高度选择性,可用于治疗靶向表达 αvβ6 的细胞。
在这篇综述中,作者讨论了导致发现 A20FMDV2 的逻辑,其立体化学在受体结合中的重要性,以及将其用作分子特异性药物递送系统的策略。这些策略包括创建 A20FMDV2-药物缀合物,基因修饰溶瘤病毒以表达 A20FMDV2,从而将其趋向性重新定向至主要表达 αvβ6 的细胞,创建表达 A20FMDV2 的 CAR T 细胞,以及通过将 A20FMDV2 插入 CDR3 环来修饰抗体的趋向性。
αvβ6 是过去几十年中发现的癌症和纤维化中最有前途的治疗靶点之一。A20FMDV2 作为分子特异性 αvβ6 靶向剂的潜在用途非常有前途,特别是考虑到该肽及其变体在临床成像中的成功。