Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future

The Journal of Clinical Investigation
Lieping Chen, Xue Han

Abstract

Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers.

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Methods Mentioned

BETA
transgenic
transfection
laser-capture microdissection

Clinical Trials Mentioned

NCT00730639
NCT01721772
NCT01844505
NCT01642004
NCT01721759
NCT01024231
NCT01295827
NCT01866319
NCT01848834
NCT01953692

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