Background: T-cell receptor alternate reading frame protein (TARP) is a novel, immunogenic 58 amino acid protein that is over-expressed in ∼95% of prostate cancer and ∼50% of breast cancer specimens and hence is a good candidate for therapeutic vaccination. In mice the immunogenicity of HLA-A*0201 binding TARP peptides can be improved through epitope-enhancement achieved by amino acid substitutions that result in increased HLA binding affinity. We conducted a first-in-human study to determine the safety and immunogenicity of TARP peptide vaccination and its impact on the velocity of PSA rise (expressed as slope log (PSA) or PSA doubling time (PSADT)) and tumor growth rate in men with Stage D0 prostate cancer.

Methods: HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) or wild type (27-35) TARP peptides administered as a peptide emulsion with Montanide ISA 51VG plus GM-CSF (Arm A) or as an autologous peptide-pulsed dendritic cell vaccine (Arm B). Vaccines were administered q 3 weeks for a total of 5 vaccines with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria and a booster dose of vaccine for all patients at 48 and 96 weeks.

Results: A total of 41 patients (n = 21 Arm A, n = 20 Arm B) enrolled, with a median on study duration of 75 weeks as of 07/31/12. Baseline cohort characteristics (median): age 62 yrs, PSA 3.44, Gleason Score 7, ALC 1270, CD4%/absolute 42.5%/547 cells/mm3, 25-OH vitamin D level 28, with 30 of 41 (73%) s/p radical prostatectomy and 26 of 41 (63%) s/p EBRT for PSA biochemical recurrence. TARP vaccination was safe and well tolerated with adverse events limited to local injection site reactions < Grade 2. Twenty-eight of 39 patients (72%) reaching 24 weeks and 23 of 31 (74%) reaching 48 weeks were documented to have a decreased slope log PSA compared to their pre-vaccination baseline (p=0.0012 and p=0.0004 for overall changes in slope log PSA, respectively); there was no statistically significant difference between the two arms, although only the DC arm was significant at 48 wks on its own. TARP vaccination also resulted in a 50% decrease in calculated tumor growth rate constant: pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p=0.003). TARP-specific IFN-γ ELISPOT responses were detected in the majority of subjects but did not correlate with observed decreases in slope log (PSA).

Citation Format: Lauren V. Wood, William L. Dahut, Antonio Fojo, James L. Gulley, Ravi Madan, Philip Arlen, Howard L. Parnes, Brenda D. Roberson, Seth M. Steinberg, Masaki Terabe, Julia Wilkerson, Ira Pastan, Jay A. Berzofsky. Autologous TARP peptide vaccination is associated with slowing in PSA velocity and a decrease in tumor growth rate in patients with Stage D0 prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4571. doi:10.1158/1538-7445.AM2013-4571