title: Intramuscular electroporation of a P1A-encoding plasmid vaccine delays P815 mastocytoma growth.
abstract: This study aimed to construct DNA vaccines encoding the mouse P1A tumor antigen and to generate a protective immune response against the P815 mastocytoma, as a model for vaccines against human MAGE-type tumor antigens. DNA vaccines were constructed and delivered to mice by intramuscular electroporation before tumor challenge. Immunization with a plasmid coding for the full-length P1A significantly delayed tumor growth and mice survived at least 10 days longer than untreated controls. 10% of the mice completely rejected the P815 tumors while 50% of them showed a regression phase followed by tumor regrowth. Mice immunized by electroporation of a P1A(35-43) minigene-encoding plasmid failed to reject tumor and even delay tumor growth. The P1A(35-43)-encoding plasmid was modified and helper epitope sequences were inserted. However, these modified plasmids were not able to improve the response against P815 mastocytoma. Consistent with these results, a 12-fold higher CTL activity was observed when the plasmid coding for full-length P1A was delivered as compared to the plasmid encoding the P1A(35-43) epitope. Our results demonstrated that electroporation is an efficient method to deliver DNA vaccines against P815 and suggested the superiority of full-length as compared to minigene constructs for DNA vaccines.
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch and de Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch and de Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: De Plaen
authors.affiliation: Ludwig Institute for Cancer Research, Brussels Branch and de Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Benoît J
authors.initials: BJ
authors.lastname: Van den Eynde
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université catholique de Louvain, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018274:Electroporation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007114:Immunization; D034801:Mastocytoma / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D019444:Vaccines, DNA
keywords: Cancer DNA vaccine; Electroporation; Electrotransfer; P1A; P815 mastocytoma