Definition

An orally bioavailable, allosteric, small molecule activator of integrin cell adhesion receptors very late antigen-4 (VLA-4; integrin alpha4/beta1) and lymphocyte function-associated antigen-1 (LFA-1; integrin alphaL/beta2), with potential immunomodulatory and antineoplastic activities. Upon oral administration, alintegimod activates VLA-4 and LFA-1 expressed on the surface of leukocytes, thereby promoting the VLA-4- and LFA-1-mediated adhesion of leukocytes to counter-receptors vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). This may promote VLA-4/VCAM-1- and LFA-1/ICAM-1-mediated cell-cell adhesion between naive T cells and antigen presenting cells (APCs) and enhance T-cell activation. The enhanced VCAM-1 and ICAM-1 binding by the activated integrins expressed on activated T cells may also promote intratumoral T-cell accumulation and infiltration. This may lead to enhanced T-cell-mediated killing of tumor cells. Integrins VLA-4 and LFA-1 are cellular adhesion molecules (CAMs) that play key roles in antigen presentation and leukocyte migration.