CD6 is a type I integral membrane glycoprotein characterized by an extracellular region containing three cysteine-rich functional domains known as SRCRs (scavenger receptor cysteine-rich), making it a member of the SRCR superfamily. CD6 is expressed on the surface of peripheral blood T cells and thymic medullary T cells, as well as on cortical thymocytes, B1 cells, certain NK cells, brain cells, and chronic leukemia cells derived from either T or B lymphocytes. CD6 plays a critical role in T-cell activation, helping to regulate T-cell functions and mediating cell-to-cell adhesion. Notably, the CD6 molecule can form a complex with the TCR/CD3 complex, contributing to the formation of the immunological synapse (IS). The mature immunological synapse is divided into two distinct regions: the central supramolecular activation cluster (C-SMAC) and the peripheral supramolecular activation cluster (P-SMAC). Among these, CD6 is a key component of the C-SMAC. The formation of the immunological synapse (IS) is a pivotal step in T-cell antigen recognition, proliferation, and activation, serving as a cornerstone of both cellular and humoral immune responses in the body. In the pathogenesis of autoimmune diseases, T-cell proliferation, activation, and migration play crucial roles. Given CD6's essential role in lymphocyte maturation, activation, and proliferation, targeting and inhibiting CD6 function offers promising new therapeutic strategies for treating autoimmune conditions such as rheumatoid arthritis and psoriasis. A humanized anti-CD6 monoclonal antibody (T1h) specifically binds to the SRCR1 domain of CD6 but does not interfere with the interaction between CD6 and its ligand ALCAM (activated leukocyte cell adhesion molecule, also known as CD166). Instead, the T1h antibody forms an immune complex with cell-surface CD6, which is subsequently internalized via endocytosis and ultimately degraded within the lysosomal system. This process effectively reduces the levels of CD6 on the lymphocyte surface, disrupting the formation of the immunological synapse between CD6 and the TCR/CD3 complex. As a result, phosphorylation of key signaling pathways such as STAT3, MAPK, and AKT is diminished, leading to suppressed lymphocyte activation and proliferation. Consequently, the expression and secretion of pro-inflammatory cytokines like IFN-γ and TNF-α are significantly reduced, thereby achieving the therapeutic goal of alleviating autoimmune disease symptoms. Currently, Phase III clinical trials evaluating T1h monoclonal antibody for the treatment of psoriasis and rheumatoid arthritis are underway. Early clinical observations indicate that T1h exhibits a favorable safety profile, with minimal adverse effects reported. Notably, over 50% of psoriasis patients have achieved substantial clinical improvement, evidenced by a PASI-75 response, while rheumatoid arthritis patients have shown significant improvements, including ACR 20 and even ACR 50/ACR 70 responses in some cases.

　　CD6 is a type I integral membrane glycoprotein characterized by an extracellular region containing three cysteine-rich functional domains known as SRCRs (scavenger receptor cysteine-rich), making it a member of the SRCR superfamily. CD6 is expressed on the surface of peripheral blood T cells and thymic medullary thymocytes, as well as on cortical thymocytes, B1 cells, certain NK cells, brain cells, and chronic leukemia cells derived from either T or B lymphocytes. CD6 plays a crucial role in T-cell activation, helping to regulate T-cell functions and mediating cell-to-cell adhesion. Notably, the CD6 molecule can form a complex with the TCR/CD3 complex, contributing to the formation of the immunological synapse (IS). The mature immunological synapse is divided into two distinct regions: the central supramolecular activation cluster (C-SMAC) and the peripheral supramolecular activation cluster (P-SMAC), with CD6 serving as a key component of the C-SMAC. The formation of the immunological synapse (IS) is a critical step in T-cell antigen recognition, proliferation, and activation, playing a pivotal role in both cellular and humoral immune responses within the body.
　　
　　In the pathogenesis of autoimmune diseases, T-cell proliferation, activation, and migration play crucial roles. Given the critical role of the CD6 molecule in lymphocyte maturation, activation, and proliferation, blocking CD6 function could offer novel therapeutic strategies and approaches for treating autoimmune conditions such as rheumatoid arthritis and psoriasis.
　　
　　The humanized anti-CD6 monoclonal antibody (T1h) binds specifically to the SRCR1 domain of CD6 but does not interfere with the interaction between the CD6 molecule and its ligand ALCAM (activated leukocyte cell adhesion molecule, also known as CD166). Instead, the immune complex formed by T1h and surface-expressed CD6 molecules is internalized via an endocytosis mechanism, ultimately delivered into the cell where it gets degraded within the intracellular lysosomal system. This process reduces the levels of CD6 on the lymphocyte surface, thereby disrupting the formation of the immunological synapse (IS) between CD6 and the TCR/CD3 complex. Consequently, T1h attenuates the phosphorylation of key signaling pathways such as STAT3, MAPK, and AKT, leading to suppressed lymphocyte activation and proliferation. Ultimately, this results in a significant downregulation of inflammatory cytokines like IFN-γ and TNF-α, effectively mitigating autoimmune responses and offering therapeutic benefits for autoimmune diseases.
　　
　　Currently, the Phase III clinical trial evaluating T1h monoclonal antibody for the treatment of psoriasis and rheumatoid arthritis is underway. Clinically, T1h monoclonal antibody has demonstrated a low incidence of adverse reactions, with over 50% of psoriasis patients achieving an objective PASI 75 response, while rheumatoid arthritis patients have shown ACR 20 clinical improvement, and some individuals have even experienced ACR50 or ACR70 improvements.