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CTLA-4 + PD-1 inhibitor refers to the combination therapy or dual-targeting agents (such as bispecific antibodies) that simultaneously inhibit cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways. CTLA-4 and PD-1 are distinct immune checkpoint receptors that negatively regulate T-cell activation at different stages and anatomical sites: CTLA-4 primarily acts during the priming phase of T-cell activation in lymphoid tissues, whereas PD-1 mainly functions during the effector phase in peripheral tissues and the tumor microenvironment. Dual blockade of these pathways provides a synergistic effect, enhancing T-cell activation, proliferation, and infiltration into tumors, thereby overcoming adaptive resistance mechanisms. This combination strategy has been widely investigated and approved for various malignancies, including melanoma, non-small cell lung cancer, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, pleural mesothelioma, and esophageal squamous cell carcinoma, using combinations such as ipilimumab plus nivolumab or tremelimumab plus durvalumab, as well as bispecific antibodies like cadonilimab.
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