How Does an Anti-CTLA-4 Antibody Promote Cancer Immunity?

Anti-CTLA-4 antibodies can induce lasting protection for some melanoma patients. However, their therapeutic potential is limited by significant immunotherapy-related adverse effects (irAE). Here, we argue that the therapeutic effect may be based on an agonist activity that is fundamentally distinct, and can be therapeutically differentiated, from the antagonist activity responsible for irAE. Anti-CTLA-4 antibodies can induce lasting protection for some melanoma patients. However, their therapeutic potential is limited by significant immunotherapy-related adverse effects (irAE). Here, we argue that the therapeutic effect may be based on an agonist activity that is fundamentally distinct, and can be therapeutically differentiated, from the antagonist activity responsible for irAE.