BACKGROUND: 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).
METHODS: 16 patients with castration-resistant, non-metastatic prostate cancer received six immunizations at two-week intervals, and then either quarterly (Arm 1) or as determined by multi-parameter 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. 6/16 (38%) remained metastasis-free at 2 years. PAP-specific T cells were elicited in 12/16 (75%), predominantly of a Th1 phenotype, which persisted in frequency and phenotype for at least one year. IFNγ-secreting T-cell responses measured by ELISPOT were detectable in 5/13 individuals at one year, and this was not statistically different between study arms. The overall median fold change in PSA DT from pre-treatment to post-treatment 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.
Written by:
McNeel DG, Becker JT, Eickhoff JC, Johnson LE, Bradley ES, Pohlkamp IF, Staab MJ, Liu G, Wilding G, Olson BM. Are you the author?
Medicine / Medical Oncology, University of Wisconsin Comprehensive Cancer Center; Department of Biostatistics & Medical Informatics, Iowa State University; Medicine, University of Wisconsin-Madison; Carbone Cancer Center, University of Wisconsin; Medicine, University of Wisconsin Comprehensive Cancer Center; Medicine, University of Wisconsin Carbone Cancer Center; Hematology-Oncology Section, UW Carbone Cancer Center.
Reference: Clin Cancer Res. 2014 May 21. pii: clincanres.0169.2014.
doi: 10.1158/1078-0432.CCR-14-0169
PubMed Abstract
PMID: 24850844
UroToday.com Prostate Cancer Immunotherapy Section
