Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors

Gang Xin, David M. Schauder, Weiqing Jing, Aimin Jiang, Nikhil S. Joshi, Bryon Johnson, Weiguo Cui*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)740-745
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number4
DOIs
StatePublished - Jan 24 2017

Keywords

  • Adoptive cell transfer
  • CD8 T cells
  • Immunotherapy
  • Listeria
  • Melanoma

ASJC Scopus subject areas

  • General

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