title: Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells.
abstract: A generally applicable, easy-to-use method of focusing a patient's immune system to eradicate or prevent cancer has been elusive. We are attempting to develop a targeted virus to accomplish these aims. We previously created a recombinant replicating vesicular stomatitis virus (VSV) that preferentially infected Her2/neu expressing breast cancer cells and showed therapeutic efficacy in an implanted Balb/c mouse tumor model. The current work shows that this therapy generated therapeutic anti-tumor CD4 T cells against multiple tumor antigens. CD4 T cells transferred directly from cured donor mice could eradicate established tumors in host mice. T cells were transferred directly from donor mice and were not stimulated ex vivo. Both tumors that expressed Her2/neu and those that did not were cured by transferred T cells. Analysis of cytokines secreted by anti-tumor memory CD4 T cells displayed a multifunctional pattern with high levels of interferon-γ, interleukin (IL)-4 and IL-17. Anti-tumor memory CD4 T cells traveled to the mesenteric lymph nodes and were activated there. Treatment with targeted recombinant replicating VSV is a potent immune adjuvant that generates therapeutic, multifunctional anti-tumor memory CD4 T cells that recognize multiple tumor antigens. Immunity elicited by viral therapy is independent of host major histocompatibility complex or knowledge of tumor antigens. Virus-induced tumor immunity could have great benefit in the prevention and treatment of tumor metastases.
authors.affiliation: Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: P
authors.initials: P
authors.lastname: Whitaker-Dowling
authors.forename: J A
authors.initials: JA
authors.lastname: Griffin
authors.forename: I
authors.initials: I
authors.lastname: Bergman
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines