title: Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors.
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.
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53213.
authors.forename: Gang
authors.initials: G
authors.lastname: Xin
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53213.|Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226.
authors.forename: David M
authors.initials: DM
authors.lastname: Schauder
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Jing
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263.
authors.forename: Aimin
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
authors.forename: Nikhil S
authors.initials: NS
authors.lastname: Joshi
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226.
authors.forename: Bryon
authors.initials: B
authors.lastname: Johnson
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53213; weiguo.cui@bcw.edu.|Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cui
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell
keywords: CD8 T cells; Listeria; adoptive cell transfer; immunotherapy; melanoma