Vargas, FA;
Furness, AJS;
Solomon, I;
Joshi, K;
Mekkaoui, L;
Lesko, MH;
Rota, EM;
... Quezada, SA; + view all
(2017)
Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
Immunity
, 46
(4)
pp. 577-586.
10.1016/j.immuni.2017.03.013.
Preview |
Text
Chester_1-s2.0-S1074761317301231-main.pdf - Published Version Download (4MB) | Preview |
Abstract
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 (FcgR) 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 antiCD25 antibody with enhanced binding to activating FcgRs 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.
Archive Staff Only
 |
View Item |
