A Bispecific Antibody Targeting the αv and α5β1 Integrins Induces Integrin Degradation in Prostate Cancer Cells and Is Superior to Monospecific Antibodies.

Fibronectin-binding integrins α5β1 and αv collaborate in prostate cancer-bone stromal interactions relevant to the colonization of the bone marrow microenvironment. Combinatorial inactivation of these integrins on prostate cancer cells was assessed. Monospecific antibodies to α5β1and αv integrins alone (MAb) and in combination (cMAb), and a bispecific antibody that simultaneously targets α5β1and αv integrins (BsAbα5β1/αv) were compared in assays of chemotaxis, clonogenic survival, and induction of endothelial migration. Cellular expression of integrins, their transcription, translation, and degradation fate was compared. The BsAbα5β1/αv was superior to MAbs and cMAbs in abrogating adhesion, migration, clonogenic survival, and induction of endothelial migration responses by prostate cancer cells. Integrin upregulation observed with MAbs or cMAbs was abrogated with the BsAbα5β1/αv. Loss of integrin expression was uniquely induced by the BsAbα5β1/αv and blocked by lysosomal inhibition. IMPLICATIONS: A novel and effective combinatorial strategy to target α5β1and αv integrins is defined for translational studies. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/1/27/F1.large.jpg. ©2019 American Association for Cancer Research.