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Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma

Nature Biotechnology volume 30, pages 337–343 (2012)Cite this article

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Abstract

Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4+ interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology.

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Figure 1: Validation of the altered self melanoma epitope VSV-cDNA library.
Figure 2: Intravenous ASMEL cures established B16 melanomas.
Figure 3: VSV functions as an hsp70-mediated adjuvant.
Figure 4: VSV-induced TGF-β masks the tumor-specific IL-17 recall response.
Figure 5: Tumor-specific immunity induced by VSV-cDNA libraries is mediated by combinations of antigens.

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Acknowledgements

We thank T. Higgins for expert secretarial assistance. This work was supported by the Richard M. Schulze Family Foundation, the Mayo Foundation, Cancer Research UK, the US National Institutes of Health grants R01 CA107082, R01CA130878 and R01 CA132734, and a grant from Terry and Judith Paul. MyD88 KO mice (MyD88−/−) were a kind gift from L. Pease, Mayo Clinic.

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Author notes

  1. Jose Pulido and Timothy Kottke: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA

    Jose Pulido, Timothy Kottke, Jill Thompson, Feorillo Galivo, Rosa Maria Diaz, Diana Rommelfanger, Elizabeth Ilett & Richard Vile

  2. Department of Ophthalmology and Ocular Oncology, Mayo Clinic, Rochester, Minnesota, USA

    Jose Pulido

  3. Virology and Cell Technology, National Center for Genetic Engineering and Biotechnology, Pathumthani, Thailand

    Phonphimon Wongthida

  4. Cancer Research UK Clinical Centre, St. James' University Hospital, Leeds, UK

    Elizabeth Ilett, Peter Selby, Alan Melcher & Richard Vile

  5. Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA

    Larry Pease & Richard Vile

  6. University of Surrey, Guildford, UK

    Hardev Pandha

  7. The Institute of Cancer Research, London, UK

    Kevin Harrington

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Contributions

J.P., T.K., J.T., F.G., P.W., R.M.D., D.R. and E.I. ran the experiments. J.P., T.K., L.P., H.P., K.H., P.S., A.M. and R.V. conceived the experimental approach and planned the experiments. J.P., T.K., H.P., K.H., P.S., A.M. and R.V. wrote the manuscript.

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Correspondence to Richard Vile.

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Pulido, J., Kottke, T., Thompson, J. et al. Using virally expressed melanoma cDNA libraries to identify tumor-associated antigens that cure melanoma. Nat Biotechnol 30, 337–343 (2012). https://doi.org/10.1038/nbt.2157

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