A modified DNA vaccine to p53 induces protective immunity to challenge with a chemically induced sarcoma cell line.
Journal - Cellular immunology (United States )
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.
|ISSN : ||0008-8749|
|Mesh Heading : ||Animals Cells, Cultured Disease-Free Survival Female Interferon-gamma Methylcholanthrene Mice Mice, Inbred BALB C Mutation Sarcoma, Experimental T-Lymphocytes Tumor Cells, Cultured Tumor Suppressor Protein p53 Viral Vaccines biosynthesis chemically induced immunology immunology analysis|
|Mesh Heading Relevant : ||Cancer Vaccines Vaccines, DNA prevention & control genetics immunology|