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Whole recombinant yeast vaccine induces antitumor immunity and improves survival in a genetically engineered mouse model of melanoma

Gene Therapy volume 18, pages 827–834 (2011)Cite this article

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Abstract

Malignant melanoma is one of the deadliest forms of skin cancer and its incidence is expected to rise over the next two decades. At present, there are no effective therapies for advanced melanoma. We have previously shown that administration of whole recombinant yeast expressing human MART-1 (hMART-IT) induces protective antimelanoma immunity in a B16F10 transplantable mouse model. In this study, we examine the effectiveness of the hMART-IT vaccine in a congenic strain of genetically engineered mouse model of melanoma, which recapitulates both the underlying genetics and the proper tumor microenvironment of naturally occurring melanoma. Subcutaneous administration of hMART-IT induced cytotoxicity against melanoma cells and antigen-specific production of Th1-specific cytokines by splenocytes. Weekly administration of hMART-IT significantly delayed the development of melanoma and prolonged the survival of mice compared with controls. Although histological analysis demonstrated diffuse infiltration of CD4+ T cells and CD8+ T cells, no reduction of regulatory T cells was observed, suggesting that hMART-IT cannot prevent immunotolerance in the tumor microenvironment. This study provides a proof of concept that genetically engineered mouse models lend valuable insights into immunotherapeutics being tested in the preclinical setting.

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Acknowledgements

This work was supported by grants to MF from the Melanoma Research Foundation and Dermatology Foundation. We thank Kayo Okamura and Dr Joe Takeo (UCD, Department of Dermatology) for their technical support. We thank Drs Donald Bellgrau, Richard Duke (UCD, Department of Immunology and Medical Oncology) and Alex Franzusoff (GlobeImmune Inc., Aurora, CO, USA) for their intellectual support. UCD flow core (Alistaire S Acosta and Karen Helm, supported by NIH grant P30 CA046934) helped with flow cytometry and cytokine analyses.

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Authors and Affiliations

  1. Department of Dermatology, University of Colorado Denver, Aurora, CO, USA

    A Tanaka, J D Jensen, R Prado, H Riemann, Y G Shellman, D A Norris & M Fujita

  2. Department of Dermatology, Wakayama Medical University, Wakayama, Japan

    A Tanaka

  3. Department of Dermatology, Harvard Medical School, Boston, MA, USA

    L Chin

  4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    C Yee

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  1. A Tanaka
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Correspondence to M Fujita.

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Tanaka, A., Jensen, J., Prado, R. et al. Whole recombinant yeast vaccine induces antitumor immunity and improves survival in a genetically engineered mouse model of melanoma. Gene Ther 18, 827–834 (2011). https://doi.org/10.1038/gt.2011.28

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