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FcyRIIB is a novel immune checkpoint in the tumor microenvironment limiting activity of Treg-targeting antibodies.

David A KnorrRom LeidnerShawn JensenRyan MengAndrew JonesCarmen Ballesteros-MerinoR Bryan BellMaria BaezDavid SprottCarlo BifulcoBrian D PieningRony DahanBernard A FoxJeffrey Ravetch
Published in: bioRxiv : the preprint server for biology (2023)
Fully human anti-CTLA-4 antibodies are limited in their capacity to deplete T regulatory cells and drive durable anti-tumor immunity in humanized FcyR/hCTLA-4 miceThe inhibitory Fcy receptor, FcyRIIB, is upregulated in the tumor microenvironment in patients and in humanized FcyR/hCTLA-4 miceBlocking FcyRIIB leads to rescue of Treg depletion in humanized murine modelsFc engineering can improve the depleting capacity and in vivo anti-tumor activity of anti-CTLA and anti-CCR8 antibodies targeting tumor infiltrating Tregs.
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