Vaccination with agonist peptide PSA:154–163(155L) derived from prostate specific antigen induced CD8 T cell response to the native peptide PSA:154–163 but failed to induce the reactivity against tumor targets expressing PSA: a Phase 2 study in patients with recurrent prostate cancer

摘要

We conducted a clinical trial of peptide PSA:154–163(155L) vaccination in HLA-A2 patients with detectable and rising serum PSA after radical prostatectomy for prostate cancer (Clinicaltrials.gov identifier ). The trial was a single dose-level, Phase II pilot trial of 1 mg of PSA154–163(155L) emulsified with adjuvant (Montanide ISA-51). The primary endpoint was determination of immunogenicity of the vaccine; secondary outcomes were determination of toxicity and effect on serum PSA. The vaccine was given subcutaneously 7 times on weeks 0, 2, 4, 6, 10, 14, and 18. Peptide-specific CD8 T-cell responses in the peripheral blood mononuclear cells (PBMC) of patients were measured by IFN-γ ELISPOT assay. CD8 T-cell cultures were also established by in vitro stimulation with the peptide presented by autologous dendritic cells. Five patients were enrolled and completed all vaccinations. No IFN-γ response to PSA:154–163(155L) was detected in unfractioned PBMC in any patient either before or after vaccination. Three of five patients demonstrated strong IFN-γ responses to PSA:154–163(155L) as well as native PSA:154–163 peptides in CD8 T-cell cultures derived from post-vaccination PBMC. However, peptide-specific T cells failed to recognize HLA-A2 targets expressing endogenous PSA. There were no significant changes in serum PSA level in any subject. No serious adverse events were observed. PSA154–163(155L) is not an effective immunogen when given with Montanide ISA-51. The PSA154–163 peptide is poorly processed from endogenous PSA and therefore represents a cryptic epitope of PSA in HLA-A2 antigen-presenting cells.