Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen Journal Article


Authors: Rafiq, S.; Purdon, T. J.; Daniyan, A. F.; Koneru, M.; Dao, T.; Liu, C.; Scheinberg, D. A.; Brentjens, R. J.
Article Title: Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen
Abstract: CD19-directed chimeric antigen receptor (CAR) T cells are clinically effective in a limited set of leukemia patients. However, CAR T-cell therapy thus far has been largely restricted to targeting extracellular tumor-associated antigens (TAA). Herein, we report a T-cell receptor-mimic (TCRm) CAR, termed WT1-28z, that is reactive to a peptide portion of the intracellular onco-protein Wilms Tumor 1(WT1), as it is expressed on the surface of the tumor cell in the context of HLA-A∗02:01. T cells modified to express WT1-28z specifically targeted and lysed HLA-A∗02:01+ WT1+ tumors and enhanced survival of mice engrafted with HLA-A∗02:01+, WT1+ leukemia or ovarian tumors. This in vivo functional validation of TCRm CAR T cells provides the proof-of-concept necessary to expand the range of TAA that can be effectively targeted for immunotherapy to include attractive intracellular targets, and may hold great potential to expand on the success of CAR T-cell therapy. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Journal Title: Leukemia
Volume: 31
Issue: 8
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2017-08-01
Start Page: 1788
End Page: 1797
Language: English
DOI: 10.1038/leu.2016.373
PROVIDER: scopus
PMCID: PMC5495623
PUBMED: 27924074
DOI/URL:
Notes: Article -- Export Date: 1 September 2017 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    198 Brentjens
  2. Tao Dao
    58 Dao
  3. Mythili Koneru
    6 Koneru
  4. Sarwish Rafiq
    12 Rafiq
  5. Terence John Purdon
    37 Purdon
  6. Anthony   Daniyan
    10 Daniyan