Cancer Immunology, Immunotherapy

, Volume 54, Issue 11, pp 1082–1094 | Cite as

Induction of Th1-type immunity and tumor protection with a prostate-specific antigen DNA vaccine

  • 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
Original Article

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 IFNγ 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.

Keywords

PSA Prostate Cynomolgus monkey Immunotherapy Genetic vaccine T helper 1 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Deborah J. Marshall
    • 1
  • Lani R. San Mateo
    • 1
  • Kelly A. Rudnick
    • 1
  • Stephen G. McCarthy
    • 1
  • Michael C. Harris
    • 1
  • Christine McCauley
    • 1
  • Allen Schantz
    • 1
  • Dong Geng
    • 1
  • Pam Cawood
    • 1
  • Linda A. Snyder
    • 1
  1. 1.Centocor Inc.RadnorUSA

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