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

• Published in: Journal of immunotherapy (1997) Vol. 32; no. 6; p. 655
• Main Authors: Kouiavskaia, Diana V, Berard, Carla A, Datena, Ellen, Hussain, Arif, Dawson, Nancy, Klyushnenkova, Elena N, Alexander, Richard B
• Format: Journal Article
• Language: English
• Published: United States 01.07.2009
• Subjects: Aged; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Humans; Interferon-gamma - immunology; Interferon-gamma - metabolism; Male; Middle Aged; Neoplasm Recurrence, Local - therapy; Peptide Fragments - adverse effects; Peptide Fragments - immunology; Peptide Fragments - therapeutic use; Pilot Projects; Prostate-Specific Antigen - adverse effects; Prostate-Specific Antigen - immunology; Prostate-Specific Antigen - therapeutic use; Prostatic Neoplasms - surgery; Prostatic Neoplasms - therapy; Vaccination
• ISSN: 1537-4513
• DOI: 10.1097/CJI.0b013e3181a80e0d

We conducted a clinical trial of peptide prostate specific antigen (PSA): 154-163 (155L) vaccination in human leukocyte antigen (HLA)-A2 patients with detectable and rising serum PSA after radical prostatectomy for prostate cancer (Clinicaltrials.gov identifier NCT00109811). The trial was a single dose-level, phase 2 pilot trial of 1 mg of PSA: 154-163 (155L) emulsified with adjuvant (Montanide ISA-51). The primary endpoint was the 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 interferon (IFN)-gamma enzyme-linked immunosorbent spot 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-gamma response to PSA: 154-163 (155L) was detected in unfractioned PBMC in any patient either before or after vaccination. Three of 5 patients demonstrated strong IFN-gamma responses to PSA: 154-163 (155L) and native PSA: 154-163 peptides in CD8 T-cell cultures derived from postvaccination PBMC. However, peptide-specific T cells failed to recognize HLA-A2 positive targets expressing endogenous PSA. There were no significant changes in serum PSA level in any subject. No serious adverse events were observed. PSA: 154-163 (155L) is not an effective immunogen when given with Montanide ISA-51. The PSA: 154-163 peptide is poorly processed from endogenous PSA and therefore represents a cryptic epitope of PSA in HLA-A2 antigen-presenting cells.