Cited by 106CAR-T cell therapy researchT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

TGF‐β–responsive CAR‐T cells promote anti‐tumor immune function

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Hou, Andrew J., Chang, ZeNan L., Lorenzini, Michael H., Zah, Eugenia, Chen, Yvonne Y.·2018·Bioengineering & Translational Medicine

Abstract

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-β CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-β CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-β CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-β CARs in the development of adoptive T-cell therapy for cancer.

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Crossref · 10.1002/btm2.10097

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  • High TGF-β signaling has been implicated in resistance to various anti-cancer treatments including chemotherapies and molecularly-targeted therapies.

    “High TGF-β signaling has been implicated in resistance to various anti-cancer treatments including chemotherapies and molecularly-targeted therapies149,380,381.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [380]

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Authors
Hou, A. J., Chang, Z. L., Lorenzini, M. H., Zah, E., & Chen, Y. Y.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Chen, Yvonne Y.
Venue
Bioengineering & Translational Medicine
Publisher
Wiley
Published
2018-05
Volume
3
Issue
2
Pages
75-86
ISSN
2380-6761 (ISSN-L)
OpenAlex
W2807108630
Cited by
106
References
49
Citations by year
2026: 5 · 2025: 11 · 2024: 19 · 2023: 15 · 2022: 22 · 2021: 14 · 2020: 10 · 2019: 8 · 2012: 1
FWCI
3.01
Type
journal article
Language
en
Open access
Locations
  • Bioengineering & Translational Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (DP5OD012133, F30CA183528, T32 GM067555)
  • National Cancer Institute
  • National Center for Advancing Translational Sciences
  • National Institute of General Medical Sciences
  • National Heart, Lung, and Blood Institute
  • NIH Office of the Director
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
chimeric antigen receptor, adoptive T cell therapy, antitumor immunity, regulatory T cells, effector T cells, TGF-beta signaling, immunosuppression, cancer immunotherapy

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