Real-time immune monitoring to guide plasmid DNA vaccination schedule targeting prostatic acid phosphatase in patients with castration-resistant prostate cancer.
OBJECTIVE
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
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.
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and dm3@medicine.wisc.edu.
Douglas G
DG
McNeel
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Jordan T
JT
Becker
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and Department of Biostatistics, University of Wisconsin, Madison, Wisconsin.
Jens C
JC
Eickhoff
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Laura E
LE
Johnson
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Eric
E
Bradley
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Isabel
I
Pohlkamp
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Mary Jane
MJ
Staab
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Glenn
G
Liu
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
George
G
Wilding
Authors' Affiliations: University of Wisconsin Carbone Cancer Center; and.
Brian M
BM
Olson
D000135:Acid Phosphatase / Q000276:immunology*; D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage*; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000008:administration & dosage*; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage*
D019496:Cancer Vaccines; D019444:Vaccines, DNA; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017430:Prostate-Specific Antigen