title: Construction of a triple modified p53 containing DNA vaccine to enhance processing and presentation of the p53 antigen.
abstract: More effective and less toxic treatments are urgently needed in the treatment of patients with cancer. The tumour suppressor protein p53 is a tumour-associated antigen that could serve that purpose when applied in an immunologic approval to cancer. It is mutated in approximately 50% of the tumours resulting in p53 overexpression, which can serve as target for therapy. To improve the immunisation results in patients with p53 overexpression tumours we constructed a DNA vaccine that could lead to improved processing and presentation of p53 peptides in the MHC-class I. We constructed a triple modified p53 fusion protein containing DNA vaccine by (1) addition of a xeno-antigen (mouse or rat p53 fragment), (2) potentiation of intra-cytoplasmatic accumulation of p53 by deleting the nuclear signalling part, (3) improving the processing to peptides of p53 by addition of ubiquitin. In-vitro experiments confirmed correct construction of the DNA vaccine. Preliminary testing in normal and HLA-A2 mice of this triple modified p53 containing DNA construct meant for human application showed a trend towards a superior immunogenicity.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen and University of Groningen, The Netherlands. g.a.p.hospers@int.umcg.nl
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
authors.forename: Coby
authors.initials: C
authors.lastname: Meijer
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Dam
authors.forename: Frank
authors.initials: F
authors.lastname: Roossink
authors.forename: Nanno H
authors.initials: NH
authors.lastname: Mulder
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D018274:Electroporation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009369:Neoplasms / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D016159:Tumor Suppressor Protein p53; D019444:Vaccines, DNA