Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells Journal Article
| Authors: | Kloss, C. C.; Condomines, M.; Cartellieri, M.; Bachmann, M.; Sadelain, M. |
| Article Title: | Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells |
| Abstract: | Current T-cell engineering approaches redirect patient T cells to tumors by transducing them with antigen-specific T-cell receptors (TCRs) or chimeric antigen receptors (CARs) that target a single antigen. However, few truly tumor-specific antigens have been identified, and healthy tissues that express the targeted antigen may undergo T cell-mediated damage. Here we present a strategy to render T cells specific for a tumor in the absence of a truly tumor-restricted antigen. T cells are transduced with both a CAR that provides suboptimal activation upon binding of one antigen and a chimeric costimulatory receptor (CCR) that recognizes a second antigen. Using the prostate tumor antigens PSMA and PSCA, we show that co-transduced T cells destroy tumors that express both antigens but do not affect tumors expressing either antigen alone. This 'tumor-sensing' strategy may help broaden the applicability and avoid some of the side effects of targeted T-cell therapies. |
| Journal Title: | Nature Biotechnology |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-01-01 |
| Start Page: | 71 |
| End Page: | 75 |
| Language: | English |
| DOI: | 10.1038/nbt.2459 |
| PROVIDER: | scopus |
| PUBMED: | 23242161 |
| PMCID: | PMC5505184 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 1 February 2013" - "CODEN: NABIF" - "Source: Scopus" |
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