Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells

Cancer Gene Ther. 2012 Apr;19(4):282-91. doi: 10.1038/cgt.2011.90. Epub 2012 Jan 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cytokines / biosynthesis
  • Female
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics*
  • Genetic Vectors / immunology
  • Humans
  • Immunologic Memory / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / genetics*
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Neoplasms / therapy
  • Vesicular stomatitis Indiana virus / genetics*
  • Vesicular stomatitis Indiana virus / immunology

Substances

  • Cytokines