Immune checkpoint inhibitors for nonsmall cell lung cancer treatment.
Immune checkpoint inhibition with blocking antibodies that target cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 (PD-1) pathway [PD-1/programmed death-ligand 1 (PD-L1)] have demonstrated promise in a variety of malignancies. While ipilimumab has been approved as a CTLA-4 blocking antibody by the US Food and Drug Administration for the treatment of advanced melanoma, it is still not approved for lung cancer treatment. In contrast, nivolumab and pembrolizumab, both PD-1 blocking antibodies, have been approved for second-line treatment of nonsmall cell lung cancer in 2015 because of their high potency and long-lasting effects in some patient subgroups. Other PD-1 and PD-L1 monoclonal antibodies are also in active development phase. Treatment with such immune checkpoint inhibitors is associated with a unique pattern of immune-related adverse events or side effects. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade or checkpoint inhibitors with chemotherapy or radiotherapy are being investigated to determine whether they may enhance the efficacy of treatment. Despite many challenges ahead, immunotherapy with checkpoint inhibitors has already become a new and important treatment modality for lung cancer in the last decade following the discovery of targeted therapy.
Division of General Chest Medicine, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Yang-Ming Medical University, Taipei, Taiwan, ROC; School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC. Electronic address: ymchen@vghtpe.gov.tw.
Yuh-Min
YM
Chen
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor; C000613593:durvalumab; D000077594:Nivolumab; C000594389:atezolizumab; C582435:pembrolizumab; C000609138:avelumab
adenocarcinoma; checkpoint inhibitor; immunotherapy; lung cancer; lymphocytes