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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.

Original publication

DOI

10.1016/j.bioelechem.2013.11.002

Type

Journal article

Journal

Bioelectrochemistry

Publication Date

12/2014

Volume

100

Pages

112 - 118

Keywords

Cancer DNA vaccine, Electroporation, Electrotransfer, P1A, P815 mastocytoma, Amino Acid Sequence, Animals, Antibodies, Neoplasm, Antigens, Neoplasm, Cell Line, Tumor, Cell Proliferation, Electroporation, Epitopes, T-Lymphocyte, Female, Immunization, Mastocytoma, Mice, Muscles, Peptide Fragments, Plasmids, T-Lymphocytes, Cytotoxic, Time Factors, Vaccines, DNA