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Publication : Induction by DNA immunization of a protective antitumor cytotoxic T lymphocyte response against a minimal-epitope-expressing tumor.

First Author  Iwasaki A Year  1998
Journal  Cancer Immunol Immunother Volume  45
Issue  5 Pages  273-9
PubMed ID  9439651 Mgi Jnum  J:45008
Mgi Id  MGI:1101618 Doi  10.1007/s002620050443
Citation  Iwasaki A, et al. (1998) Induction by DNA immunization of a protective antitumor cytotoxic T lymphocyte response against a minimal-epitope-expressing tumor. Cancer Immunol Immunother 45(5):273-9
abstractText  In order to examine the use of DNA immunization to block tumor growth, we have developed a model system in which a defined 9-amino-acid epitope from the nucleoprotein of influenza virus is used as a surrogate tumor-associated antigen. A mastocytoma cell line of DBA/2 origin (P815) was transfected with a plasmid encoding the minimal H-2Kd-restricted NP(147-155) cytotoxic T lymphocyte (CTL) epitope, pCMV/NPep, to generate the cell line designated P815-NPep. Mice primed and boosted once with a plasmid encoding the full-length NP gene, pCMV/NP, but not with the minigene pCMV/NPep, developed a strong NP(147-155)-specific CTL response within 2 weeks after the boost. When challenged with 10(4) P815-NPep cells, pCMV/NP-immunized DBA/2 mice were protected from tumor challenge, whereas control mice immunized with the vector backbone rapidly developed lethal tumor. Importantly, the P815-NPep-immune mice were also protected from a subsequent challenge with the untransfected parental tumor P815. By depleting the NP-immune mice of either CD4+ or CD8+ T cells and then challenging with 10(4) P815-NPep tumor cells, it was determined that the CD8-depleted mice rapidly developed tumors, whereas the CD4-depleted or non-treated mice were protected. These data clearly indicate that intramuscular (i.m.) plasmid DNA immunization can be used to mobilize an effective CD8+ CTL-mediated antitumor response.
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