Induction of Th1-type immunity and tumor protection with a prostate-specific antigen DNA vaccine |
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Authors: | Deborah J. Marshall Lani R. San Mateo Kelly A. Rudnick Stephen G. McCarthy Michael C. Harris Christine McCauley Allen Schantz Dong Geng Pam Cawood Linda A. Snyder |
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Affiliation: | (1) Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087, USA |
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Abstract: | Prostate specific antigen (PSA) is a serum marker that is widely used in the detection and monitoring of prostate cancer. Though PSA is a self-antigen, T cell responses to PSA epitopes have been detected in healthy men and prostate cancer patients, suggesting it may be used as a target for active immunotherapy of prostate cancer. A PSA DNA vaccine (pPSA) was evaluated in mice and monkeys for its ability to induce antigen-specific immune responses. Mice immunized intradermally with pPSA demonstrated strong PSA-specific humoral and cellular immunity. The anti-PSA immune responses were skewed toward Th1, as shown by high IFN and IL-2 production. The immune response was sufficient to protect mice from challenge with PSA-expressing tumor cells. Tumor protection was durable in the absence of additional vaccination, as demonstrated by protection of vaccinated mice from tumor rechallenge. Furthermore, pPSA vaccination induced PSA-specific antibody titers in male cynomolgus monkeys, which express a closely related PSA gene. These results demonstrate that vaccination with pPSA may be able to break tolerance and can induce an immune response that mediates tumor protection. |
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Keywords: | PSA Prostate Cynomolgus monkey Immunotherapy Genetic vaccine T helper 1 |
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