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-Db-restricted epitope PSA(65-73) (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/PSA65-73 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 PSA65-73-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.
Written by:
Klyushnenkova EN, Kouiavskaia DV, Parkins CJ, Caposio P, Botto S, Alexander RB, Jarvis MA. Are you the author?
Department of Surgery, Division of Urology, University of Maryland, Baltimore, MD 21201, USA.
Reference: J Immunother. 2012 Jun;35(5):390-9.
doi: 10.1097/CJI.0b013e3182585d50
PubMed Abstract
PMID: 22576344
UroToday.com Investigative Urology Section