Abstract 5520: Therapeutic vaccination with epitope-enhanced and wild-type TARP peptides in stage D0 prostate cancer

Abstract

Abstract Background: T-cell receptor alternate reading frame protein (TARP) is immunogenic, is expressed in ∼95% of prostate cancer specimens and hence is a good candidate for therapeutic vaccination. 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 and immunogenicity at least in mice. We conducted a pilot study to determine the safety and immunogenicity of TARP peptide vaccination and its impact on PSA doubling time (PSADT) 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 are 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 weeks. Results: 26 patients have enrolled in the study to date (n = 14 Arm A, n = 12 Arm B) with a mean on study duration of 7.5 months. Mean baseline cohort characteristics: age 63 yrs, PSA 4.43, PSADT 7.3 months and Gleason Score 6.7 with 19 of 26 s/p radical prostatectomy. TARP vaccination was safe and well tolerated with adverse events limited to local injection site reactions < Grade 2. Nine of 18 patients (50%) reaching 24 weeks on study were documented to have an increase in their PSADT compared to baseline. Mean Percent Increase/Prolongation in PSADT: Surprisingly TARP-specific IFN-γ ELISPOT responses have been detected ex vivo in only 3 of 14 (21%) patients examined to date. Conclusion: Vaccination with wild type and epitope-enhanced TARP peptides results in prolongation of PSADT in a substantial fraction of patients. The immunologic correlates responsible for PSADT lengthening are poorly understood and require additional study. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5520. doi:10.1158/1538-7445.AM2011-5520