CD6, a surface glycoprotein of T cells, is a rheostat-type signalosome that tunes T cell activation. It belongs to the superfamily of scavenger receptor cysteine-rich (SRCR) glycoproteins. CD6 has determinant roles in thymocyte development, T cell activation, and immune responses. CD6 modulates signaling during T cell development as the lack of CD6 changes the threshold for negative selection in the thymus. This results in a reduced number of T cells that fully mature. Mice with disrupted Cd6 genes display differing responses in the two main inflammatory disease settings investigated so far. In the collagen-induced arthritis model, Cd6 knockout mice were characterized by earlier disease onset, increased clinical score, and worsened hallmarks for the disease. However, in a model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), the absence of CD6 confers resistance to the demyelinating disorder.
Inhibitory Antibodies are mAbs that are very efficient in research of cancer, immunology, and infection. These mAbs bind monospecifically to certain cells or proteins, thus stimulating the immune system by blocking specific cell receptors. Bughani et al. have developed an anti-mouse CD6 mAb, mCD6D1, that recognizes the membrane distal domain of CD6, to ameliorate the incidence of EAE in C57BL/6 mice. Meanwhile, Li et al. have used a mouse anti-human CD6-d1 mAb, UMCD6, to reverse EAE progression in DBA/1 humanized mice.
Itolizumab is a humanized recombinant IgG1 monoclonal antibody (mAb).
Itolizumab (Anti-Human CD6 Recombinant Antibody) acts by binding to scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6. Thus, Itolizumab downregulates the gene transcription of pro-inflammatory cytokines and adhesion molecules, including IFN-γ, IL-6, and TNF-α. Therefore, Itolizumab shows therapeutic efficiency in a humanized xenograft mouse model of Graft Vs Host Disease (GVHD). Following the in vivo experiment results, it decreases mortality compared to the vehicle (100% vs. 10%). Importantly, Itolizumab is very efficient in research of autoimmune pathologies, such as arthritis and psoriasis, yielding very encouraging results.
All in all, Itolizumab is a humanized recombinant anti-CD6 mAb that acts by binding to SRCR distal domain 1 of CD6.