Harnessing the power of foot-and-mouth-disease virus for targeting integrin alpha-v beta-6 for the therapy of cancer

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.