In this review we highlight a unique dual effect of blocking the CD6/CD318 interaction with UMCD6, an anti-CD6 mAb known to block T-cell dependent autoimmunity through effects on differentiation of effector CD4+T cell subsets, while also activating the anti-cancer cytotoxic properties of CD8+T and NK cells (Figure 2). Here, CDCP1 is linked to cancer.