Challenges to Prostate Cancer Immunotherapy

Klyushnenkova, Elena N.; Alexander, Richard B.

doi:10.5772/28762

Advancements in Tumor Immunotherapy and Cancer Vaccines 2012

DOI: 10.5772/28762

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Challenges to Prostate Cancer Immunotherapy

Elena N. Klyushnenkova¹,

Richard B. Alexander²

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2012

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Cited by 1 publication

References 61 publications

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A Cytomegalovirus-based Vaccine Expressing a Single Tumor-specific CD8+ T-cell Epitope Delays Tumor Growth in a Murine Model of Prostate Cancer

Klyushnenkova

Kouiavskaia

Parkins

et al. 2012

Journal of Immunotherapy

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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 to 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 (DR2b×PSA F1). We assessed the capacity of two 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 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/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 anti-tumor 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.

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A Cytomegalovirus-based Vaccine Expressing a Single Tumor-specific CD8+ T-cell Epitope Delays Tumor Growth in a Murine Model of Prostate Cancer

Klyushnenkova

Kouiavskaia

Parkins

et al. 2012

Journal of Immunotherapy

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Challenges to Prostate Cancer Immunotherapy

Cited by 1 publication

References 61 publications

A Cytomegalovirus-based Vaccine Expressing a Single Tumor-specific CD8+ T-cell Epitope Delays Tumor Growth in a Murine Model of Prostate Cancer

A Cytomegalovirus-based Vaccine Expressing a Single Tumor-specific CD8+ T-cell Epitope Delays Tumor Growth in a Murine Model of Prostate Cancer

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