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

Perambakam S, Hallmeyer S, Reddy S, Mahmud N, Bressler L, DeChristopher P, Mahmud D, Nunez R, Sosman JA, Peace DJ
Cancer Immunol Immunother. 2006 55 (9): 1033-42

PMID: 16283303 · DOI:10.1007/s00262-005-0090-x

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.

MeSH Terms (20)

Aged Aged, 80 and over Amino Acid Sequence Cancer Vaccines Dendritic Cells Epitopes Humans Hypersensitivity, Delayed Immunity, Cellular Immunotherapy, Active Male Middle Aged Molecular Sequence Data Peptide Fragments Peptides Prostate-Specific Antigen Prostatic Neoplasms T-Lymphocytes, Cytotoxic T-Lymphocyte Subsets Transplantation, Autologous

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