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Real-time immune monitoring to guide plasmid DNA vaccination schedule targeting prostatic acid phosphatase in patients with castration-resistant prostate cancer.

McNeel DG, Becker JT, Eickhoff JC, Johnson LE, Bradley E, Pohlkamp I, Staab MJ, Liu G, Wilding G, Olson BM.

Clin Cancer Res. 2014 Jul 15;20(14):3692-704.

Comment from Henk van der Poel:
Vaccinations for prostate cancer with both ProstVac and Sipuleucel-T have shown a benefit for survival without apparent delays in progression-free survival in clinical trials. Since clinical progression was not associated with survival in these studies and prolonged vaccination may improve immunization monitoring of vaccination efficacy. McNeel et al. showed PAP-specific T-cells in the majority of men treated with DNA vaccines but failed to associate these with clinical outcome and vaccination scheme.

Abstract

PURPOSE:

We have previously reported that a DNA vaccine encoding prostatic acid phosphatase (PAP) could elicit PAP-specific T cells in patients with early recurrent prostate cancer. In the current pilot trial, we sought to evaluate whether prolonged immunization with regular booster immunizations, or "personalized" schedules of immunization determined using real-time immune monitoring, could elicit persistent, antigen-specific T cells, and whether treatment was associated with changes in PSA doubling time (PSA DT).

EXPERIMENTAL DESIGN:

Sixteen patients with castration-resistant, nonmetastatic prostate cancer received six immunizations at 2-week intervals and then either quarterly (arm 1) or as determined by multiparameter immune monitoring (arm 2).

RESULTS:

Patients were on study a median of 16 months; four received 24 vaccinations. Only one event associated with treatment >grade 2 was observed. Six of 16 (38%) remained metastasis-free at 2 years. PAP-specific T cells were elicited in 12 of 16 (75%), predominantly of a Th1 phenotype, which persisted in frequency and phenotype for at least 1 year. IFNγ-secreting T-cell responses measured by ELISPOT were detectable in 5 of 13 individuals at 1 year, and this was not statistically different between study arms. The overall median fold change in PSA DT from pretreatment to posttreatment was 1.6 (range, 0.6-7.0; P = 0.036).

CONCLUSIONS:

Repetitive immunization with a plasmid DNA vaccine was safe and elicited Th1-biased antigen-specific T cells that persisted over time. Modifications in the immunization schedule based on real-time immune monitoring did not increase the frequency of patients developing effector and memory T-cell responses with this DNA vaccine.

©2014 American Association for Cancer Research.

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