Anti-ITGA4 Antibody (Natalizumab)

Natalizumab is a humanized monoclonal IgG4 antibody that selectively targets ITGA4 (integrin alpha 4, also known as CD49d). It blocks the interaction of as alpha4beta1 (VLA-4) with vascular cell adhesion molecule VCAM-1, intercellular adhesion molecule ICAM-1, and fibronectin by competitively binding to the alpha4 subunit. Integrin alpha 4 beta 7 (alpha4beta7) is also known as Lymphocyte Peyer's patch adhesion molecule-1 (LPAM-1), a heterodimer composed of the integrin beta 7 subunit (ITGB7) and the ITGA44 subunit (also known as CD49d or integrin alpha 4), of interest in studies of the gastrointestinal tissue. Key interactions include surface adhesion molecules such as MADCAM1 (mucosal vascular addressin cell adhesion molecule 1) and VCAM (vascular cell adhesion molecule), as well as fibronectin. This protein has been linked to diseases such as UC (ulcerative colitis) and Crohn's disease, amongst others. There are several approved LPAM-1 targeting therapeutics, such as vedolizumab (commercially known as Entyvio, Takeda), that aim to mitigate inflammatory bowel disease and cancer, with more clinical trials underway. Natalizumab, a monoclonal antibody that targets ITGA4, is currently sold under the brand name Tysabri, for relapsing forms of MS (multiple sclerosis) and Chrohn's disease.