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      Cytomegalovirus containing TRP2 antigen provides protective immunity against the poorly immunogenic B16BL6-D5 melanoma

      , 1 , 1 , 4 , 4 , 2 , 4 , 3 , 1 , 4

      Journal for Immunotherapy of Cancer

      BioMed Central

      Society for Immunotherapy of Cancer 28th Annual Meeting

      8-10 November 2013

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          Cytomegalovirus is known to induce long-lived humoral and cellular immune responses that persist and increase over time. In humans on average more than 5% of T cells are CMV-reactive. We have previously reported that mouse cytomegalovirus (MCMV) encoding the unmodified TRP2 protein can induce immunity that protects mice from challenge with the weakly immunogenic B16-F10 melanoma [Xu 2013]. This protective immunity could be induced in mice with pre-existing immunity to MCMV, overcoming a critical hurdle to the clinical application of this strategy. Surprisingly, this immunity to TRP2 was mediated by antibody. We have extended these observations to the poorly immunogenic B16BL6-D5 (D5) melanoma model, where we now report that vaccination also provides protective immunity. While anti-TRP2 immunity induced by MCMV is humoral, it is as effective as vaccination with a GM-CSF-secreting (GVAX) vaccine (D5-G6) that induces tumor-specific T cell immunity. When we evaluated MCMV-TRP2 in a therapeutic model, the vaccine was ineffective as a single agent. We went on to investigate whether the "inflating" immunity that MCMV is well known for would lead to the co-development of a T cell response long-term. Mice were vaccinated with MCMV-TRP2 and followed long-term. Half of these mice were challenged with viable D5 on day 14. Controls included mice that were vaccinated with D5-G6 and followed long-term. After more than 190 days from the initial vaccination, mice were sacrificed and spleen and lymph node cells were interrogated for an IFN-γ response following stimulation with D5, murine sarcoma cells, or a peptide specific for MCMV. As expected, a large IFN-γ response was elicited by the MCMV peptide in MCMV-vector immunized mice. In addition all vaccinated animals developed a detectable IFN-γ response to the D5 melanoma. The intensity of the T cell response was similar in mice receiving MCMV-TRP2 and D5-G6. Studies are ongoing to characterize the targets of this T cell response and evaluate the mechanism(s) of MCMV-TRP2-induced tumor elimination. While preliminary, the well-established ability of CMV to induce and maintain high-frequency antigen-specific responses, combined with our results, suggest that this strategy may provide an opportunity to augment the anti-cancer immune responses.

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          Author and article information

          J Immunother Cancer
          J Immunother Cancer
          Journal for Immunotherapy of Cancer
          BioMed Central
          7 November 2013
          : 1
          : Suppl 1
          : P271
          [1 ]Laboratory of Molecular and Tumor Immunology, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center, Portland, OR, USA
          [2 ]Laboratory of Cancer Immunobiology, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center, Portland, OR, USA
          [3 ]Department of Pathology, Providence Cancer Center, Portland, OR, USA
          [4 ]Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
          Copyright © 2013 Neuberger et al; licensee BioMed Central Ltd.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

          Society for Immunotherapy of Cancer 28th Annual Meeting
          National Harbor, MD, USA
          8-10 November 2013
          Poster Presentation


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