DNA fusion gene vaccines induce cytotoxic T-cell attack on naturally processed peptides of human prostate-specific membrane antigen
| Autor: | Christian H. Ottensmeier, Jason Rice, Elena Harden, Gisella E. Vittes, Freda K. Stevenson |
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| Rok vydání: | 2011 |
| Předmět: |
Cytotoxicity
Immunologic Glutamate Carboxypeptidase II Male Recombinant Fusion Proteins Molecular Sequence Data Immunology Antigen presentation Epitopes T-Lymphocyte Enzyme-Linked Immunosorbent Assay CD8-Positive T-Lymphocytes urologic and male genital diseases Cancer Vaccines Epitope Interferon-gamma Mice Tetanus Toxin Antigen Cell Line Tumor HLA-A2 Antigen MHC class I Vaccines DNA Animals Humans Immunology and Allergy Cytotoxic T cell Amino Acid Sequence Antigen-presenting cell HLA-A Antigens biology Vaccination Prostatic Neoplasms Molecular biology Mice Inbred C57BL Antigens Surface biology.protein Peptide vaccine Peptides CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | European Journal of Immunology. 41:2447-2456 |
| ISSN: | 0014-2980 |
| Popis: | For long-term attack on tumor cells in patients with prostate cancer, induction of cytolytic T cells is desirable. Several lineage-specific target proteins are known and algorithms have identified candidate MHC class I-binding peptides, particularly for HLA-A*0201. We have designed tolerance-breaking DNA fusion vaccines incorporating a domain of tetanus toxin fused to candidate tumor-derived peptide sequences. Using three separate peptide sequences from prostate-specific membrane antigen (PSMA) (peptides PSMA(27) , PSMA(663) , and PSMA(711) ), this vaccine design induced high levels of CD8(+) T cells against each peptide in a HLA-A(*) 0201 preclinical model. In contrast, the full-length PSMA sequence containing all three epitopes was poorly immunogenic. Induced T cells were cytotoxic against peptide-loaded tumor cells, but only those against PSMA(27) or PSMA(663) peptides, and not PSMA(711) , were able to kill tumor cells expressing endogenous PSMA. Cytotoxicity was also evident in vivo. The preclinical model provides a powerful tool for generating CD8(+) T cells able to predict whether target cells can process and present peptides, essential for planning peptide vaccine-based clinical trials. |
| Databáze: | OpenAIRE |
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