Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146–154 peptide
| Autor: | Samarth Reddy, Sigrun Hallmeyer, Phillip J. DeChristopher, Nadim Mahmud, Supriya Perambakam, Linda R. Bressler, Rafael Nunez, Delores Mahmud, David Peace, Jeffrey A. Sosman |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment T cell Molecular Sequence Data Immunology Cancer Vaccines Transplantation Autologous Epitopes Immune system Antigen T-Lymphocyte Subsets medicine Humans Immunology and Allergy Hypersensitivity Delayed Amino Acid Sequence Antigen-presenting cell Aged Aged 80 and over Immunity Cellular business.industry Immunotherapy Active Prostatic Neoplasms Dendritic Cells Immunotherapy T lymphocyte Dendritic cell Middle Aged Prostate-Specific Antigen Peptide Fragments medicine.anatomical_structure Oncology Peptides business CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Immunology, Immunotherapy. 55:1033-1042 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-005-0090-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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