Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors
Name
Xin-2017-Pathogen boosted adoptive cell transf.pdf
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Author(s)
Xin, Gang
Schauder, David M.
Jing, Weiqing
Jiang, Aimin
Johnson, Bryon
Cui, Weiguo
Joshi, Nik
Date Issued
January 2017
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Xin, Gang, et al. “Pathogen Boosted Adoptive Cell Transfer Immunotherapy to Treat Solid Tumors.” Proceedings of the National Academy of Sciences 114, no. 4 (January 2017): 740–745 © 2017 National Academy of Sciences
Version
Final published version
Abstract
Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1614315114
