Lifitegrast (SAR 1118) is an Integrin LFA-1 (αLβ2) Antagonist

Lymphocyte function-associated antigen 1 (LFA-1; αLβ2) is a key T cell integrin, which plays an important role in regulating T cell activation and migration. Specifically, LFA-1 belongs to the integrin superfamily of adhesion molecules. Besides, LFA-1 is one of the first cell surface molecules by monoclonal antibodies against leukocyte immunogen. Moreover, LFA-1 plays a key role in migration. Furthermore, LFA-1 also mediates the arrest of leukocytes. In addition, LFA-1 is important in cytotoxic T cell-mediated killing and granulocyte and monocyte-mediated antibody killing.

Meanwhile, LFA-1 is relevant to a variety of autoimmune and inflammatory diseases, including inflammatory bowel disease, psoriasis, diabetes, and arthritis. Nonetheless, LFA-1-mediated adhesion plays an important role in the extravasation of immature and activated T cells into lymph nodes and tissues, respectively. Dysregulation of LFA-1 expression can lead to changes in T cell activation and differentiation. The stable involvement of LFA-1 / ICAM-1 is important to re-strengthen many pathways to achieve complete T cell differentiation. Anti LFA-1 has become a potential but still largely undeveloped immunotherapy. Here, we will introduce an LFA-1 (αLβ2) antagonist, Lifitegrast.

Lifitegrast (SAR 1118) is an Integrin LFA-1 (αLβ2) Antagonist.

Firstly, Lifitegrast is an LFA-1 antagonist and inhibits Jurkat T cell attachment to ICAM-1 with an IC50 of 2.98 nM. Importantly, Lifitegrast inhibits T cell-mediated inflammation by blocking the binding of two important cell surface proteins (lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1). Thus, Lifitegrast reduce s overall inflammatory responses. Lifitegrast strongly inhibits Jurkat T cell attachment to ICAM-1.

Secondly, Lifitegrast (SAR 1118) has potent anti-inflammatory activity on corneal inflammation with the optimal application being a 1% solution in either 2 or 3 times prior. Corneal inflammation is induced by antibiotic-killed P. aeruginosa and S. aureus in the presence of a silicone hydrogel lens. Particularly, Lifitegrast ophthalmic drops administered thrice daily deliver therapeutic levels of Lifitegrast in the retina. Obviously, this can alleviate the retinal complications associated with diabetes.

All in all, Lifitegrast is an integrin LFA-1 (αLβ2) antagonist.


Perez VL, et al. Ocul Surf. 2016 Apr;14(2):207-15.