%0 Journal Article
%T Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody
%A Andrew C. Scott
%A Annamalai Selvakumar
%A Casey A. Jarvis
%A Cheng Liu
%A Claire Oh
%A David A. Scheinberg
%A Elliott J. Brea
%A Lianxing Liu
%A Manuel Guerreiro
%A Martin G. Klatt
%A Sung Soo Mun
%A Tao Dao
%A Tatyana Korontsvit
%A Zhiyuan Yang
%J Archive of "Oncoimmunology".
%D 2019
%R 10.1080/2162402X.2019.1570778
%X Depletion of T regulatory cells (Tregs) in the tumor microenvironment is a promising cancer immunotherapy strategy. Current approaches for depleting Tregs are limited by lack of specificity and concurrent depletion of anti-tumor effector T cells. The transcription factor forkhead box p3 (Foxp3) plays a central role in the development and function of Tregs and is an ideal target in Tregs, but Foxp3 is an intracellular, undruggable protein to date. We have generated a T cell receptor mimic antibody, ˇ°Foxp3-#32,ˇ± recognizing a Foxp3-derived epitope in the context of HLA-A*02:01. The mAb Foxp3-#32 selectively recognizes CD4 + CD25 + CD127low and Foxp3 + Tregs also expressing HLA-A*02:01 and depletes these cells via antibody-mediated cellular cytotoxicity. Foxp3-#32 mAb depleted Tregs in xenografts of PBMCs from a healthy donor and ascites fluid from a cancer patient. A TCRm mAb targeting intracellular Foxp3 epitope represents an approach to deplete Tregs
%K Immunosuppression
%K Tregs
%K Foxp3
%K TCRm mAb
%K immunotherapy
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527296/