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Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors. Proc Natl Acad Sci U S A 2017 01 24;114(4):740-745

Date

01/11/2017

Pubmed ID

28069963

Pubmed Central ID

PMC5278465

DOI

10.1073/pnas.1614315114

Scopus ID

2-s2.0-85010648441   8 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.

Author List

Xin G, Schauder DM, Jing W, Jiang A, Joshi NS, Johnson B, Cui W

Author

Weiguo Cui PhD Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
CD8-Positive T-Lymphocytes
Cancer Vaccines
Cell Line, Tumor
Immunologic Memory
Immunotherapy, Adoptive
Mice
Mice, Inbred C57BL
Neoplasms
Receptors, Antigen, T-Cell
T-Lymphocytes, Cytotoxic
jenkins-FCD Prod-400 0f9a74600e4e79798f8fa6f545ea115f3dd948b2