UBC Faculty Research and Publications

Indoleamine Dioxygenase Inhibitors : Clinical Rationale & Current Development Zhu, Mayanne; Dancsok, Amanda R.; Nielsen, Torsten


Purpose of review: This review focuses on the recent clinical development of indolamine-2,3- dioxygenase-1 (IDO-1) inhibitors. Recent findings: IDO-1 alters tryptophan metabolism in a manner enhancing T-regulatory cell activity, but pre-clinical data show that its role in tumorigenesis is context-dependent on host and tumor interaction, highlighting some challenges in understanding the molecular oncology of this enzymatic drug target. Because results from phase I/II trials of IDO-1 inhibitor monotherapy have been disappointing, current clinical trials employ IDO-1 inhibitors in combination strategies with other immunotherapy agents or with chemotherapy +/- radiation. Combinations with anti PD-1/PD-L1 antibodies are already showing promise, and related strategies are under active evaluation. Summary: While further research is needed to elucidate the precise role of IDO-1 in tumor development, its mechanisms of action appear sufficiently distinct from other immunotherapy targets to warrant inclusion in combination immunotherapy regimens, an approach where multiple clinical trials are currently underway.

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