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Integrin subunit beta 6 (ITGB6) is a transmembrane protein that exclusively pairs with the alpha-v subunit to form the heterodimeric integrin αvβ6 receptor (UniProt P18564). This receptor is primarily expressed on epithelial cells and serves as a critical regulator of cell-matrix interactions and the activation of latent transforming growth factor-beta (TGF-β) (PubMed: 25135935). While ITGB6 expression is low or absent in most healthy adult tissues, it is significantly upregulated during wound healing, inflammation, and in various epithelial-derived malignancies (PubMed: 31434711). In cancer, ITGB6 promotes tumor progression, invasion, and metastasis by facilitating epithelial-to-mesenchymal transition and modulating the tumor microenvironment. Sigvotatug vedotin (SGN-B6A) is an investigational antibody-drug conjugate (ADC) that targets ITGB6 to deliver a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE), directly to tumor cells (ClinicalTrials.gov: NCT04389632). By leveraging the restricted expression of ITGB6 in normal tissues compared to its high expression in tumors, this therapeutic approach aims to maximize anti-tumor activity while minimizing systemic toxicity.
Sigvotatug vedotin is an antibody-drug conjugate (ADC) that binds to Integrin subunit beta 6 (ITGB6) on the cell surface, leading to internalization and the release of the microtubule-disrupting agent monomethyl auristatin E (MMAE), which induces cell cycle arrest and apoptosis (ClinicalTrials.gov: NCT04389632).
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