title: A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer.
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 PSA(65-73) (mCMV/PSA(65-73)) or the full-length gene for PSA (mCMV/PSA(FL)) 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/PSA(FL) 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/PSA(FL) 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.
authors.affiliation: Department of Surgery, Division of Urology, University of Maryland, Baltimore, MD 21201, USA. eklyushnenkova@smail.umaryland.edu
authors.forename: Elena N
authors.initials: EN
authors.lastname: Klyushnenkova
authors.forename: Diana V
authors.initials: DV
authors.lastname: Kouiavskaia
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Parkins
authors.forename: Patrizia
authors.initials: P
authors.lastname: Caposio
authors.forename: Sara
authors.initials: S
authors.lastname: Botto
authors.forename: Richard B
authors.initials: RB
authors.lastname: Alexander
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jarvis
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016366:Open Reading Frames; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000517:prevention & control*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D047368:Tumor Burden; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; D017430:Prostate-Specific Antigen