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Odulimomab Overview

Introduction of Odulimomab

Odulimomab is jointly developed by Immunotech and Sanofi Genzyme as a CD11a antigen antagonists. Odulimomab is a monoclonal antibody therapeutic drug for the prevention of transplant rejection and for the treatment of various immunological diseases. It is a murine IgG1 monoclonal antibody directly against the alpha chain of the protein lymphocyte function-associated antigen 1 (LFA-1).  LFA-1 is comprised of two components, CD11a and CD18 (beta 2 chain, ITGB2). The CD11a antigen, also known as Integrin alpha L and ITGAL, is encoded by ITGAL gene. It is an adhesion molecules and involved in cellular adhesion and costimulatory signaling. Odulimomab is designed as anti-CD11a therapeutic drug investigated in the transplant immunosuppression. The initial clinical studies of odulimomab is in bone marrow and kidney transplant settings. It has been reported that the previously study of odulimomab had found it was effect in the treatment of steroid-resistant graft-versus-host, and it seems to increase the rate of engraftment in children receiving non-identical bone marrow grafts. However, the treatment for acute kidney graft rejection of odulimomab is not beneficial just the same with results from animal models. Although induction therapy with odulimomab showed a trend toward a reduced rate of delayed graft function in renal transplant patients, the results had not been observed in the clinical trials. At present, the development of odulimomab has been discontinued.

Mechanism of Action of Odulimomab

Odulimomab is a monoclonal antibody drug against LFA-1. More accurately, it is for α chain of LFA-1(CD11a). LFA-1 is a cell adhesion molecule on lymphocytes and plays an important roles in regulating T cell activation and migration. Additionally, it regulates the immune cell development, localization, and pathogen clearance. LFA-1 also has been implicated in many autoimmune and inflammatory diseases such as inflammatory bowel disease, psoriasis, diabetes, and arthritis due to its diversity. However, the downstream signaling pathways activated by LFA-1 is highly conserved between migration, T cell activation. LFA-1 is a cell surface heterodimer glycoprotein composed of two non-covalently bonded submonomers, α- and β- subunits. The α chain of LFA-1 is known as CD11a or integrin alpha L. It had been anti-CD11a antibodies repressed T cell proliferation induced by the stimulation of mitogens, anti-CD3 antibodies and allogeneic cells in vitro studies. And when added more early, the effect is better, which suggests that anti-CD11a mAb might affect the early proliferation of T cell. The monoclonal antibody of CD11a has been shown efficacy in same mice models of autoimmune disease and transplantation like collagen-induced arthritis, heart allografts, and lupus. Odulimomab is one of the antibody drugs. It targets CD11a antigen of LFA-1 to prevent transplant rejection.

Mechanism of Action of Odulimomab Fig.1 Mechanism of Action of Odulimomab

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