Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide.

Abstract

T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4+CD8-, CD4-CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4-CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile.

• Authors: Supriya Perambakam, Sigrun Hallmeyer, Samarth Reddy, Nadim Mahmud, Linda Bressler, Phillip DeChristopher, Delores Mahmud, Rafael Nunez, Jeffrey A Sosman, David J Peace
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 55 Issue 9 Pg. 1033-42 (Sep 2006) ISSN: 0340-7004 [Print] Germany
• PMID: 16283303 (Publication Type: Clinical Trial, Phase I, Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cancer Vaccines
• Epitopes
• Peptide Fragments
• Peptides
• prostate-specific antigen (146-154)
• Prostate-Specific Antigen

Topics

• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Cancer Vaccines (administration & dosage, immunology)
• Dendritic Cells (cytology, immunology, transplantation)
• Epitopes
• Humans
• Hypersensitivity, Delayed (immunology)
• Immunity, Cellular
• Immunotherapy, Active (methods)
• Male
• Middle Aged
• Molecular Sequence Data
• Peptide Fragments (administration & dosage, immunology)
• Peptides (administration & dosage, immunology)
• Prostate-Specific Antigen (administration & dosage, immunology)
• Prostatic Neoplasms (immunology, therapy)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Transplantation, Autologous