Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
Arce Vargas, F
Miranda Rota, E
Ben Aissa, A
Werner Sunderland, M
Melanoma TRACERx Consortium
Renal TRACERx Consortium
Lung TRACERx Consortium
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CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.
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Fc gamma receptors
inhibitory Fc receptor
regulatory T cells
Cell Line, Tumor
Immunoglobulin Fc Fragments
Interleukin-2 Receptor alpha Subunit
Programmed Cell Death 1 Receptor
Melanoma and Kidney Cancer
License start date
Immunity, 46 (4), pp. 577 - 586
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
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