A modified DNA vaccine to p53 induces protective immunity to challenge with a chemically induced sarcoma cell line
| Autor: | Hildegund C.J. Ertl, Honying Deng, Zhi Quan Xiang, Wynetta Giles-Davis, Insug O, Dariusz W. Kowalczyk, Magdalena Blaszczyk-Thurin |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
T-Lymphocytes
Immunology Biology medicine.disease_cause Cancer Vaccines Disease-Free Survival Virus DNA vaccination Interferon-gamma Mice chemistry.chemical_compound Tumor Cells Cultured Vaccines DNA medicine Animals Cells Cultured Mice Inbred BALB C Mutation Viral Vaccine Point mutation Viral Vaccines Virology Molecular biology Fusion protein chemistry Cell culture Female Sarcoma Experimental Tumor Suppressor Protein p53 Vaccinia Methylcholanthrene |
| Zdroj: | Cellular Immunology. 215:20-31 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/s0008-8749(02)00004-7 |
| Popis: | Different vaccine constructs based on DNA vaccines and viral recombinant vaccines expressing mouse p53 were compared for induction of protective immune responses to challenge with a sarcoma cell line that expresses high levels of mutated p53 protein. Viral recombinant vaccines based on E1-deleted adenovirus or vaccinia virus recombinants expressing p53 with wild-type sequences in the mutational hotspot domain and a single mutation in the tetramerization domain (p53(mu338)) failed to induce protection against progression of this tumor cell line. A DNA vaccine expressing a form of p53 carrying the same point mutations as the tumor cell line showed low efficacy that was comparable to that of a DNA vaccine expressing p53(mu338). Efficacy of the DNA vaccine was augmented upon expressing p53(mu338) as a fusion protein linked to a viral leader sequence. Other modifications such as fusion to the signal sequence of the lysosome-associated membrane protein (LAMP) or ubiquitin failed to improve the efficacy of the vaccine to p53. Protection mediated by CD4(+) and CD8(+) T cells was specific for p53. |
| Databáze: | OpenAIRE |
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