A modified DNA vaccine to p53 induces protective immunity to challenge with a chemically induced sarcoma cell line.
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.
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia 19104, USA.
Honying
H
Deng
Dariusz
D
Kowalczyk
InSug
I
O
Magdalena
M
Blaszczyk-Thurin
Zhi
Z
Quan Xiang
Wynetta
W
Giles-Davis
Hildegund C J
HC
Ertl
D000818:Animals; D019496:Cancer Vaccines; D002478:Cells, Cultured; D018572:Disease-Free Survival; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics* / Q000276:immunology*; D019444:Vaccines, DNA; D014765:Viral Vaccines
D019496:Cancer Vaccines; D016159:Tumor Suppressor Protein p53; D019444:Vaccines, DNA; D014765:Viral Vaccines; D008748:Methylcholanthrene; D007371:Interferon-gamma