CTL response and protection against P815 tumor challenge in mice immunized with DNA expressing the tumor-specific antigen P815A
| Autor: | Donna M. D'Agostino, Paola Zanovello, Antonio Rosato, Beatrice Macino, Dino Collavo, Gabriella Milan, Annalisa Zambon, Vincenzo Ciminale |
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| Rok vydání: | 1997 |
| Předmět: |
medicine.drug_class
Cell Transplantation chemical and pharmacologic phenomena Biology Monoclonal antibody Epitope Mice Immune system Antigen Antigens Neoplasm Neoplasms Genetics medicine Tumor Cells Cultured Cytotoxic T cell Animals Humans Molecular Biology Transfection Molecular biology CTL Mice Inbred DBA Molecular Medicine Female Immunization Clone (B-cell biology) Plasmids T-Lymphocytes Cytotoxic |
| Zdroj: | Human gene therapy. 8(12) |
| ISSN: | 1043-0342 |
| Popis: | A DNA immunization approach was used to induce an immune response against the tumor-specific antigen P815A in DBA/2 mice. The P1A gene, which encodes the P815A antigen, was modified by the addition of a short sequence coding for a tag epitope recognized by the monoclonal antibody AU1, and cloned into the eukaryotic expression vector pBKCMV, resulting in plasmid pBKCMV-P1A. L1210 cells stably transfected with pBKCMV-P1A expressed P1A mRNA and were lysed by the syngeneic P815A-specific cytotoxic clone CTL-P1:5, thus confirming that the tag-modified P1A protein underwent correct processing and presentation. A single intramuscular injection of 100 microg of pBKCMV-P1A induced the expression of P1A mRNA for at least 4 months. Eighty percent of DBA/2 mice injected three times with 100 microg of pBKCMV-P1A generated cytotoxic T lymphocytes (CTL) that lysed P815 tumor cells, whereas mock-inoculated animals failed to show any cytotoxicity. Moreover, experiments designed to evaluate the protection of pBKCMV-P1A-immunized mice against a lethal challenge with P815 tumor cells showed that 6 of 10 immunized mice rejected the tumor, and 2 mice showed prolonged survival compared to control animals. |
| Databáze: | OpenAIRE |
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