期刊论文详细信息
Journal for ImmunoTherapy of Cancer
Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine
Jens C. Eickhoff1  Ellen Wargowski1  Mary Jane Staab1  Lauren Delmastro1  Douglas G. McNeel1  Glenn Liu1  Laura E. Johnson1 
[1] University of Wisconsin Carbone Cancer Center;
关键词: Sipuleucel-T;    DNA vaccine;    Prostate cancer;    Prostatic acid phosphatase;    Immune monitoring;    Clinical trial;   
DOI  :  10.1186/s40425-018-0333-y
来源: DOAJ
【 摘 要 】

Abstract Background Prostatic acid phosphatase (PAP) is a prostate tumor antigen, and the target of the only FDA-approved anti-tumor vaccine, sipuleucel-T. We have previously reported in two clinical trials that a DNA vaccine encoding PAP (pTVG-HP) could elicit PAP-specific, Th1-biased T cells in patients with PSA-recurrent prostate cancer. In the current pilot trial we sought to evaluate whether this vaccine could augment PAP-specific immunity when used as a booster to immunization with sipuleucel-T in patients with metastatic, castration-resistant prostate cancer (mCRPC). Methods Eigthteen patients with mCRPC were randomized to receive sipuleucel-T alone or followed by intradermal immunization with pTVG-HP DNA vaccine. Patients were followed for time to progression, and immune monitoring was conducted at defined intervals. Results Overall, patients were followed for a median of 24 months. 11/18 patients completed treatments as per protocol. No treatment-associated events > grade 2 were observed. Th1-biased PAP-specific T-cell responses were detected in 11/18 individuals, and were not statistically different between study arms. Higher titer antibody responses to PAP were detectable in patients who received pTVG-HP booster immunizations. Median time to progression was less than 6 months and not statistically different between study arms. The median overall survival for all patients was 28 months. Conclusions These findings suggest that prime-boost vaccination can augment and diversify the type of immunity elicited with anti-tumor vaccination in terms of T-cell and humoral immunity. Future studies will explore DNA as priming immunization rather than a booster immunization. Trial registration NCT01706458.

【 授权许可】

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