To evaluate T cell responses to antigens expressed on commensal bacteria and apply this phenomenon for tumor targeting, Chen et al. expressed OVA antigens on S. epidermidis (S. epi-OVA). Either as a prophylactic or therapeutic, S. epi-OVA colonization (presence on the skin without breaching the epithelial barrier) reduced outgrowth of OVA-expressing B16-F0 tumors, requiring both CD4+ and CD8+ OVA antigens on the S. epi cell wall. Treatment mobilized OVA-specific T cells to subcutaneous or metastatic tumor sites. S. epi expressing B16-F10 neoantigens also restrained tumor growth, and S. epi-OVA plus ICB therapy rejected B16-OVA tumors with protective memory against rechallenge.
Contributed by Alex Najibi
ABSTRACT: Certain bacterial colonists induce a highly specific T cell response. A hallmark of this encounter is that adaptive immunity develops preemptively, in the absence of an infection. However, the functional properties of colonist-induced T cells are not well defined, limiting our ability to understand anticommensal immunity and harness it therapeutically. We addressed both challenges by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, engineered S. epidermidis elicits tumor-specific T cells that circulate, infiltrate local and metastatic lesions, and exert cytotoxic activity. Thus, the immune response to a skin colonist can promote cellular immunity at a distal site and can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal.
Author Info: (1) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 9430
Author Info: (1) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA 94121, USA. (2) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (3) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (4) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (5) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (6) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (7) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (8) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (9) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. (10) Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. (11) Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. ChEM-H Institute, Stanford University, Stanford, CA 94305, USA. Chan Zuckerberg Biohub, Stanford, CA 94305, USA.
