The mechanistic basis of anti-CD6 as a novel form for the treatment of autoimmune diseases and cancer
Background: The use of Immune Checkpoint Inhibitors (ICIs) is limited by the induction of immune-related adverse events. CD6 is expressed by most T lymphocytes and a subset of natural killer (NK) cells, and engages the ligands CD166/ALCAM and CD318. Interrupting CD6 interaction with its ligands using UMCD6 (anti-CD6) reverses autoimmunity in mouse models of rheumatoid arthritis, multiple sclerosis and uveitis, due to suppression of differentiation of effector Th1 and Th17 cells. Recently, we have demonstrated that UMCD6 directly activates CD8+T and NK cells, enhancing these cells to kill breast, lung, and prostate cancer lines, even more robustly than ICIs directed to the PD-1/PD-1L pathway. We now explore the mechanisms by which UMCD6 activates NK cells while controlling the differentiation of CD4 cells.



