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: Diana V Kouiavskaia, Carla A Berard, Ellen Datena, Arif Hussain, Nancy Dawson, Elena N Klyushnenkova, Richard B Alexander
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2009 Jul-Aug Vol. 32 Issue 6 Pg. 655-66 ISSN: 1537-4513 [Electronic] United States
• PMID: 19483644 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Peptide Fragments
• prostate-specific antigen (154-163)
• Interferon-gamma
• Prostate-Specific Antigen

Topics

• Aged
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (adverse effects, therapeutic use)
• Cell Line, Tumor
• Humans
• Interferon-gamma (immunology, metabolism)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (therapy)
• Peptide Fragments (adverse effects, immunology, therapeutic use)
• Pilot Projects
• Prostate-Specific Antigen (adverse effects, immunology, therapeutic use)
• Prostatic Neoplasms (surgery, therapy)
• Vaccination