A Randomized, Placebo-Controlled Phase II Study of Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

TARP

• T-cell receptor g alternate reading frame protein (TARP) is a 58 amino acid protein expressed by both normal and malignant prostate cancer tissue; 95% of prostate cancer specimens are positive for TARP expression. TARP is highly expressed in prostate cancers of all Gleason types, in primary as well as metastatic disease, and in hormone sensitive and castrate resistant prostate cancer. Therefore, TARP is an ideal tumor antigen target for a vaccine.
• A prospective, randomized pilot study of 1st generation TARP Peptide vaccination (National Cancer Institute (NCI) 09-C-0139) utilizing TARP WT 27-35 and EE29-37-9V peptides was conducted in human leukocyte antigen serotype within the HLA-A serotype group (HLA-A 0201) positive men with stage D0 prostate cancer (prostate specific antigen (PSA) biochemical recurrence) and a PSA doubling time (PSADT) of greater than or equal to 3 months and less than or equal to 15 months. TARP vaccination was found to be immunogenic, safe and well tolerated, with adverse events limited to injection site reactions less than or equal to Grade 2. TARP vaccination was also associated with a decreased slope log PSA compared to pre-vaccination baseline in 72% of subjects reaching 24 weeks and 74% reaching 48 weeks (p=0.0012 and p=0.0004 for overall changes in slope log PSA, respectively); 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 interferon gamma (IFN-g) enzyme-linked immune absorbent spot (ELISPOT) responses were detected in the majority of subjects but did not correlate with decreases in slope log (PSA).

Multi-Epitope (ME) TARP Vaccine

• The vaccine platform includes the original two 9-mer HLA-A*0201 binding TARP peptide epitopes (WT27-35 and EE29-37-9V) utilized in NCI 09-C-0139 as well as an additional five 20-mer TARP peptides overlapping by 10 amino acids for a total of 7 peptides that span the amino acid sequence of the entire TARP protein.
• The advantage of this multi-epitope TARP peptide vaccine platform is that the overlapping epitopes cover the entire TARP protein, resulting in potential for induction of a multi-valent anti-TARP response. In addition, these longer synthetic peptides include TARP-specific major histocompatibility complex (MHC)class II cluster of differentiation 4 (CD4)+ T cell helper epitopes that will allow generation of better cluster of differentiation 8 (CD8)+ T cell responses with improved functional avidity and longevity as well as humoral anti-TARP antibody responses.

Study Objectives: