TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer.
T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks. 41 patients enrolled with median on-study duration of 75 weeks at the time of this analysis. Seventy-two percent of patients reaching 24 weeks and 74% reaching 48 weeks had a decreased Slope Log(PSA) compared to their pre-vaccination baseline (p = 0.0012 and p = 0.0004 for comparison of overall changes in Slope Log(PSA), respectively). TARP vaccination also resulted in a 50% decrease in median tumor growth rate (g): pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p = 0.003). 80% of subjects exhibited new vaccine-induced TARP-specific IFNγ ELISPOT responses but they did not correlate with decreases in Slope Log(PSA). Thus, vaccination with TARP peptides resulted in significant slowing in PSA velocity and reduction in tumor growth rate in a majority of patients with PSA biochemical recurrence.
Vaccine Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Lauren V
LV
Wood
Genitourinary Malignancies Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Antonio
A
Fojo
Vaccine Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Brenda D
BD
Roberson
Vaccine Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Meghan S B
MS
Hughes
Genitourinary Malignancies Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
William
W
Dahut
Genitourinary Malignancies Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
James L
JL
Gulley
Genitourinary Malignancies Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Ravi A
RA
Madan
Genitourinary Malignancies Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Philip M
PM
Arlen
Cell Processing Section, Department of Transfusion Medicine, NIH Clinical Center , Bethesda, MD, USA.
Marianna
M
Sabatino
Cell Processing Section, Department of Transfusion Medicine, NIH Clinical Center , Bethesda, MD, USA.
David F
DF
Stroncek
Cell Processing Section, Department of Transfusion Medicine, NIH Clinical Center , Bethesda, MD, USA.
Luciano
L
Castiello
Developmental Therapeutics Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Jane B
JB
Trepel
Developmental Therapeutics Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Min-Jung
MJ
Lee
Division of Cancer Prevention, NCI , Bethesda, MD, USA.
Howard L
HL
Parnes
Biostatistics and Data Management Section, Center for Cancer Research, NCI , Bethesda, MD, USA.
Seth M
SM
Steinberg
Vaccine Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Masaki
M
Terabe
Genitourinary Malignancies Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Julia
J
Wilkerson
Laboratory of Molecular Biology, Center for Cancer Research, NCI , Bethesda, MD, USA.
Ira
I
Pastan
Vaccine Branch, Center for Cancer Research, NCI , Bethesda, MD, USA.
Jay A
JA
Berzofsky
PSA biochemical recurrence; Prostate cancer; TARP; therapeutic cancer vaccine