Cytomegalovirus-based cancer vaccines expressing TRP2 induce rejection of melanoma in mice

Guangwu Xu, Tameka Smith, Finn Grey, Ann B. Hill

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Cytomegalovirus (CMV) induces strong and long-lasting immune responses, which make it an attractive candidate for a cancer vaccine vector. In this study, we tested whether a tumor antigen expressed in CMV can induce a strong anti-tumor effect. We expressed an unmodified melanoma antigen, mouse tyrosinase-related protein 2 (TRP2), in mouse cytomegalovirus (MCMV). Prophylactic vaccination of the mice with a single dose of MCMV-TRP2 induced rejection of B16 melanoma challenge; therapeutic vaccination with MCMV-TRP2 prolonged the survival of the mice challenged with B16 cells. Additionally, vaccination with MCMV-TRP2 five months before tumor challenge still induced tumor rejection, which indicated that the vaccine induced long-term protection. Furthermore, MCMV-TRP2 protected mice against B16 melanoma challenge regardless of the pre-existing CMV infection. We found that vaccination with MCMV-TRP2 induced long-lasting TRP2 specific antibodies but not CD8 T cells. In addition, depletion of CD4 and CD8 T cells did not compromise the antitumor effect by MCMV-TRP2; while in B cell deficient (μMT) mice, the vaccine lost its antitumor effect. These results indicate that antibodies, not T cells, are important in mediating the antitumor effect during the effector phase by the vaccine. We also made a spread deficient MCMV-TRP2 lacking the essential glycoprotein gL, which showed a similar antitumor effect. In conclusion, our study indicates that tumor antigen (TRP2) expressed in MCMV induces a strong and long-lasting anti-melanoma effect through an antibody-dependent mechanism. Our findings demonstrate that CMV might be a promising vector for the development of cancer vaccines.

Original languageEnglish (US)
Pages (from-to)287-291
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume437
Issue number2
DOIs
StatePublished - Jul 26 2013

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Keywords

  • Cancer vaccine
  • Cytomegalovirus
  • Melanoma
  • Tyrosinase related protein 2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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