Abstract:
Introduction: 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.Areas covered: 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.Expert opinion: 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.
摘要:
简介:整联蛋白αvβ6是一个有希望的治疗靶标,因为它在健康组织中的表达有限,在癌症和纤维化中的过度表达显著。来自口蹄疫病毒的肽A20FMDV2,对αvβ6是高度选择性的,并且可以在治疗上用于靶向表达αvβ6的细胞。涵盖的领域:在这篇评论中,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,遗传修饰溶瘤病毒以表达A20FMDV2,从而将其向性重定向到主要表达αvβ6的细胞,产生表达A20FMDV2的CAR-T细胞,并通过将A20FMDV2插入CDR3环中来修饰抗体嗜性。专家观点:αvβ6是近几十年来发现的最有希望的癌症和纤维化治疗靶点之一。A20FMDV2作为分子特异性αvβ6靶向剂的潜在用途非常有前景,特别是当考虑到肽及其变体在临床成像中的成功时。