A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity
| Autor: | Massimo Tommasino, Sandra Caldeira, Stefan Faath, Wolfram Osen, Tanja Peiler, Martin Müller, Peter Öhlschläger, Nico Michel, Lutz Gissmann, Ingrid Jochmus |
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| Rok vydání: | 2001 |
| Předmět: |
T cell
Papillomavirus E7 Proteins Biology Epitope law.invention Cell Line Mice Antigen law medicine Vaccines DNA Cytotoxic T cell Animals Papillomavirus Vaccines General Veterinary General Immunology and Microbiology Papillomavirus Infections Public Health Environmental and Occupational Health Viral Vaccines Transfection 3T3 Cells Oncogene Proteins Viral Virology DNA shuffling Mice Inbred C57BL CTL Tumor Virus Infections Infectious Diseases medicine.anatomical_structure Cell Transformation Neoplastic Recombinant DNA Cancer research Molecular Medicine Immunization Plasmids T-Lymphocytes Cytotoxic |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0264-410X |
| Popis: | Vaccination with oncogene-derived DNA for anti-cancer treatment carries a risk of de-novo tumor induction triggered by the persisting recombinant DNA. We hypothesized that an oncoprotein whose primary sequence has been rearranged (‘shuffled’) to maintain all possible T cell epitopes still induces cytotoxic T cells against the authentic protein but is devoid of transforming properties. As a model antigen, we used the E7 oncoprotein of the human papillomavirus (HPV) type 16, the major cause of cervical cancer. We have generated an artificial E7 molecule in which four domains were rearranged and, in order to maintain all possible T cell epitopes, certain sequences were duplicated. Upon transfection of this shuffled E7 gene (E7SH) into RMA cells, presentation of an E7 Db-restricted T cell epitope was shown by an E7-specific CTL line in vitro. Immunization of C57BL/6 mice with E7SH DNA induced E7-specific CTL and also conveyed protection against E7-positive syngeneic tumor cells. No transforming activity of E7SH DNA in NIH3T3 cells was detected, as determined by focus formation, induction of S-phase under conditions of serum deprivation and degradation of endogenous pRB. Our results suggest that DNA shuffling may become a promising concept for DNA-based anti-cancer vaccines. |
| Databáze: | OpenAIRE |
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