Immune Checkpoint Blockade in Cancer Therapy.
Immunologic checkpoint blockade with antibodies that target cytotoxic T lymphocyte associated antigen 4 (CTLA 4) and the programmed cell death protein 1 pathway (PD 1/PD L1) have demonstrated promise in a variety of malignancies. Ipilimumab (CTLA 4) and pembrolizumab (PD 1) are approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways. Treatment with both CTLA 4 and PD 1/PD L1 blockade is associated with a unique pattern of adverse events called immune related adverse events, and occasionally, unusual kinetics of tumor response are seen. Combination approaches involving CTLA 4 and PD 1/PD L1 blockade are being investigated to determine whether they enhance the efficacy of either approach alone. Principles learned during the development of CTLA 4 and PD 1/PD L1 approaches will likely be used as new immunologic checkpoint blocking antibodies begin clinical investigation.
Journal of clinical oncology official journal of the American Society of Clinical Oncology