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Prostate stem cell antigen DNA vaccination breaks tolerance to self-antigen and inhibits prostate cancer growth.

Molecular therapy : the journal of the American Society of Gene Therapy (2009-04-02)
Sarfraz Ahmad, Garrett Casey, Paul Sweeney, Mark Tangney, Gerald C O'Sullivan
ABSTRACT

Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal human prostate and over expressed in prostate cancer. Elevated levels of PSCA protein in prostate cancer correlate with increased tumor stage/grade, with androgen independence and have higher expression in bone metastases. In this study, the PSCA gene was isolated from the transgenic adenocarcinoma mouse prostate cell line (TRAMPC1), and a vaccine plasmid construct was generated. This plasmid PSCA (pmPSCA) was delivered by intramuscular electroporation (EP) and induced effective antitumor immune responses against subcutaneous TRAMPC1 tumors in male C57 BL/6 mice. The pmPSCA vaccination inhibited tumor growth, resulting in cure or prolongation in survival. Similarly, the vaccine inhibited metastases in PSCA expressing B16 F10 tumors. There was activation of Th-1 type immunity against PSCA, indicating the breaking of tolerance to a self-antigen. This immunity was tumor specific and was transferable by adoptive transfer of splenocytes. The mice remained healthy and there was no evidence of collateral autoimmune responses in normal tissues. EP-assisted delivery of the pmPSCA evoked strong specific responses and could, in neoadjuvant or adjuvant settings, provide a safe and effective immune control of prostate cancer, given that there is significant homology between human and mouse PSCA.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Insulin from bovine pancreas, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Insulin from bovine pancreas, ≥25 USP units/mg (HPLC), powder
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Insulin from bovine pancreas, Hybri-Max, powder, suitable for hybridoma