A cytomegalovirus-based vaccine expressing a single tumor-specific CD8 + T-cell epitope delays tumor growth in a murine model of prostate cancer

Elena N. Klyushnenkova, Diana V. Kouiavskaia, Christopher J. Parkins, Patrizia Caposio, Sara Botto, Richard B. Alexander, Michael A. Jarvis

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Cytomegalovirus (CMV) is a highly immunogenic virus that results in a persistent, life-long infection in the host typically with no ill effects. Certain unique features of CMV, including its capacity to actively replicate in the presence of strong host CMV-specific immunity, may give CMV an advantage compared with other virus-based vaccine delivery platforms. In the present study, we tested the utility of mouse CMV (mCMV)-based vaccines expressing human prostate-specific antigen (PSA) for prostate cancer immunotherapy in double-transgenic mice expressing PSA and HLA-DRB1*1501 (DR2bxPSA F1 mice). We assessed the capacity of 2 mCMV-based vectors to induce PSA-specific CD8 T-cell responses and affect the growth of PSA-expressing Transgenic Adenocarcinoma of the Mouse Prostate tumors (TRAMP-PSA). In the absence of tumor challenge, immunization with mCMV vectors expressing either a H2-D b-restricted epitope PSA65-73 (mCMV/PSA65-73) or the full-length gene for PSA (mCMV/PSAFL) induced comparable levels of CD8 T-cell responses that increased (inflated) with time. Upon challenge with TRAMP-PSA tumor cells, animals immunized with mCMV/PSA 65-73 had delay of tumor growth and increased PSA-specific CD8 T-cell responses, whereas animals immunized with mCMV/PSAFL showed progressive tumor growth and no increase in number of splenic PSA 65-73-specific T cells. The data show that a prototype CMV-based prostate cancer vaccine can induce an effective antitumor immune response in a "humanized" double-transgenic mouse model. The observation that mCMV/PSAFL is not effective against TRAMP-PSA is consistent with our previous findings that HLA-DRB1*1501-restricted immune responses to PSA are associated with suppression of effective CD8 T-cell responses to TRAMP-PSA tumors.

Original languageEnglish (US)
Pages (from-to)390-399
Number of pages10
JournalJournal of Immunotherapy
Volume35
Issue number5
DOIs
StatePublished - Jun 1 2012

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Keywords

  • Cancer vaccine
  • Cytomegalovirus
  • HLA-DR2 transgenic mice
  • Prostate cancer
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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