Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand-receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors. Antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) were the first immunotherapeutics that achieved the US Food and Drug Administration approval. Preliminary clinical results with the blockers of additional immune checkpoint proteins, such as programmed cell death protein 1 (PD-1) indicate extensive and different chances to boost antitumor immunity with the objective of conferring permanent clinical effects. This study provides an overview of the immune checkpoint pathways, including CTLA-4, PD-1, lymphocyte activation gene 3, T-cell immunoglobulin and mucin domain 3, B7-H3, and diacylglycerol kinase α and implications of their inhibition in the cancer therapy.
Keywords: B7-H3; CTAL-4; DGK-α; LAG-3; PD-1; Tim-3; antibody; immune checkpoint.
© 2018 Wiley Periodicals, Inc.