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

Cancer Gene Therapy volume 19, pages 282–291 (2012)Cite this article

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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.

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Acknowledgements

This study was supported in part by NIH Grant number RO1 CA104404. The contents of this study are solely the responsibility of the authors and do not necessarily represent the official views of the granting institution. We thank Drs Wei-Zen Wei, John K Rose, Irvin SY Chen, James P Allison and Genentech who very generously supplied materials as noted in the text. We thank Erich Scheller for technical assistance.

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Authors and Affiliations

  1. Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA

    Y Gao & J A Griffin

  2. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    P Whitaker-Dowling

  3. Departments of Pediatrics, Neurology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    I Bergman

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Correspondence to I Bergman.

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Gao, Y., Whitaker-Dowling, P., Griffin, J. et al. Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells. Cancer Gene Ther 19, 282–291 (2012). https://doi.org/10.1038/cgt.2011.90

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