Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody Journal Article

   


Authors: Dao, T.; Mun, S. S.; Scott, A. C.; Jarvis, C. A.; Korontsvit, T.; Yang, Z.; Liu, L.; Klatt, M. G.; Guerreiro, M.; Selvakumar, A.; Brea, E. J.; Oh, C.; Liu, C.; Scheinberg, D. A.
Article Title: Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody
Abstract: 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, “Foxp3-#32,” recognizing a Foxp3-derived epitope in the context of HLA-A*02:01. The mAb Foxp3-#32 selectively recognizes CD4 + CD25 + CD127 low 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. © 2019, © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
Keywords: immunotherapy; immunosuppression; foxp3; tregs; tcrm mab
Journal Title: OncoImmunology
Volume: 8
Issue: 7
ISSN: 2162-4011
Publisher: Landes Bioscience  
Date Published: 2019-01-01
Start Page: e1570778
Language: English
DOI: 10.1080/2162402x.2019.1570778
PROVIDER: scopus
PMCID: PMC6527296
PUBMED: 31143508
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064453837&doi=10.1080%2f2162402X.2019.1570778&partnerID=40&md5=fa148dbd11ddddb9d0855590f67db40b
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. David Scheinberg
    499 Scheinberg
  2. Tao Dao
    81 Dao
  3. Annamalai Selvakumar
    68 Selvakumar
  4. Tatyana Korontsvit
    53 Korontsvit
  5. Andrew Crosbie Scott
    14 Scott
  6. Elliott Joseph Brea
    17 Brea
  7. Claire Oh
    7 Oh
  8. Casey Jarvis
    5 Jarvis
  9. Manuel Guerrero
    3 Guerrero
  10. Martin Gunther Klatt
    22 Klatt
  11. Sung Soo Mun
    19 Mun
Related MSK Work