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Publication : Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity.

First Author  Disis ML Year  2003
Journal  Mol Cancer Ther Volume  2
Issue  10 Pages  995-1002
PubMed ID  14578464 Mgi Jnum  J:86498
Mgi Id  MGI:2680245 Citation  Disis ML, et al. (2003) Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity. Mol Cancer Ther 2(10):995-1002
abstractText  DNA vaccines are ideally suited for immunizing against tumor antigens because constructs can be formulated that not only encode the tumor antigen but also encode molecules chosen to improve the ability to elicit an antitumor response. Ligands expressed on antigen-presenting cells associated with stimulating a robust T-cell response are excellent candidates for inclusion in a DNA vaccine. Mice transgenic for the HER-2/neu homologue, rat neu, were immunized with full-length rat neu cDNA given alone or in combination with plasmids encoding costimulatory molecules CD80 or CD86 and the ligand for CD137 (CD137L). Intradermal injection of the plasmid constructs resulted in both plasmid transcript and antigen protein expression being detected in lymph nodes draining the injection site. Immunization with plasmids encoding the neu antigen along with plasmids encoding CD137L and either CD80 or CD86 resulted in the generation of neu-specific antibodies that induced phopshorylation of the neu tyrosine kinase and inhibited the growth of cultured tumor cells overexpressing neu. Survival of animals was significantly prolonged after immunization with vaccines encoding neu together with the costimulatory molecules. Although tumors eventually occurred in the vaccinated animals, they were markedly infiltrated with CD4+ T cells. DNA vaccines encoding neu, when given in combination with both CD137L and either CD80 or CD86, can induce cellular and humoral immunity and result in an antitumor effect.
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