Evaluating the therapeutic potential of anti-CD6 monoclonal antibody therapy in inflammatory barrier diseases. (R-12905)

Leukocyte migration is a critical step in the inflammatory response. Under pathophysiological conditions, such as chronic inflammation, endothelial cells are activated and the barrier function of the endothelium becomes impaired, leading to uncontrolled leukocyte migration traffic. A subset of immune cells that express high levels of CD6, are implicated in a range of autoimmune diseases, including psoriasis, inflammatory bowel disease and multiple sclerosis. ALCAM (Activated Leukocyte Cell Adhesion Molecule) and CD318, the CD6 counter-ligands, are broadly expressed on endothelial and epithelial cells and several studies suggest that they are involved in leukocyte trafficking. Itolizumab (also known as T1h) is a humanized IgG1 monoclonal antibody targeting the extracellular membrane-distal domain 1 of the human CD6 molecule developed at the Center of Molecular Immunology in Havana, Cuba. In spite of the well-known evidence about the role of itolizumab (anti-CD6 monoclonal antibody) as immune response regulator through more than one immunologic way: activation and proliferation of T lymphocyte and cytokine production, its impact on migration and also its effect on immune cell function and signaling pathways remain unknown. Therefore, inhibiting ALCAM-CD6 and CD318-CD6 interactions with anti-CD6 antibody itolizumab could selectively inhibit effector cell activation and trafficking into tissues, while sparing regulatory T cells, which has the potential to promote immune tolerance and induce durable disease remission. If successful, inhibition of this interaction using itolizumab can be a first step to develop a new therapeutic strategy for autoimmune and inflammatory diseases.

Keywords:immunology

Disciplines:Adaptive immunology, Applied immunology, Autoimmunity

Project type:Collaboration project