title: 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.
abstract: 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.
authors.affiliation: Division of Urology, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Diana V
authors.initials: DV
authors.lastname: Kouiavskaia
authors.forename: Carla A
authors.initials: CA
authors.lastname: Berard
authors.forename: Ellen
authors.initials: E
authors.lastname: Datena
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Nancy
authors.initials: N
authors.lastname: Dawson
authors.forename: Elena N
authors.initials: EN
authors.lastname: Klyushnenkova
authors.forename: Richard B
authors.initials: RB
authors.lastname: Alexander
mesh_terms: D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000601:surgery / Q000628:therapy*; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; C544012:prostate-specific antigen (154-163); D007371:Interferon-gamma; D017430:Prostate-Specific Antigen