Would you share the latest news on anti-PD-1 antibody and its significance to melanoma?

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KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified) ) - 08 / 06 / 2012

Anti-PD-1 antibody is a new fully human monoclonal antibody that targets the programmed-death receptor on activated cytotoxic T lymphocytes, blocking its interaction with the ligand PD-L1 (B7-H1) and thus interfering with the negative signaling in the T cells that occurs upon engagement of PD-1 with PD-L1-expressing tumors. The resulting rescue of melanoma antigen-specific T cells allows them to carry out their cytotoxic function against tumor cells, and the presence of the ligand on tumor may act as a biomarker predicting the likelihood of clinical benefit from treatment with the antibody (that is, the more dependent this failure of the immune system to control cancer is on PD-L1-PD-1 interactions, the better chance that blocking this interaction will help restore the immune system’s control of cancer). Clinical trials have begun with Phase I dose escalation followed by expansions into several diseases, and promising activity has been observed in advanced melanoma patients who had not previously received ipilimumab. Nearly 1/3 of patients experienced objective responses, many of which were quite durable, and few toxicities occurred. In particular, the blockade of PD-1 interacting with its ligand appears to avoid the widespread, non-specific immune-related toxicities associated with ipilimumab therapy that apparently result from a generalized release of cytotoxic T cells from physiologic (and pathologic) checkpoints on their activity.
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