Year: 2018
Type: article
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.
DOI: 10.1002/btm2.10097
Institution: University of California, Los Angeles
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences, Clinical and Translational Science Institute, University of California, Los Angeles
Awards: Engineering robust adoptive T-cell cancer therapy by rewiring TGF-beta signaling, Biotechnology Training in Biomedical Sciences and Engineering, G562934659, Engineering of computational receptors and gene circuits for T-cell immunotherapy, UC BRAID Center for Accelerated Innovation, Cancer Center Support Grant, UCLA Clinical and Translational Science Institute
OpenAlex ID: W2807108630