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- Title
IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice.
- Authors
Song, K; Chang, Y; Prud’homme, G J
- Abstract
Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA humoral, T-helper-1 and cytotoxic T lymphocyte (CTL) responses, and resistance to a CEA/LLC tumor challenge such that 80% of mice remained tumor free. Injection of the IL-12 plasmid alone was not protective. To analyze immune requirements, we immunized gene knockout (KO) mice of C57BL/6 background, deficient in either CD3, CD4, CD8, interferon γ (IFNγ), perforin or Fas ligand (FasL). Only CD3[sup +] mice expressing both CD4 and CD8, which appear equally important, as well as IFNγ and perforin, could fully resist a tumor challenge. IL-12 stimulated CTL activity, which was strictly CD3/CD8/perforindependent. FasL-KO mice had normal CTL activity and tumor resistance, indicating that only the perforin lyric pathway was involved. CD4-KO and IFNγ-KO mice still generated CTLs. CEA-stimulated IFN7 production occurred in both CD4- or CD8-KO mice and in both cases was augmented by IL-12. In IFNγ-KO mice, IL-12 still enhanced antiCEA antibody production but only moderately restored impaired DTH and tumor resistance. We conclude that the immune requirements for tumor rejection are stringent, involving multiple mechanisms which are all enhanced by IL12.
- Subjects
INTERLEUKIN-12; DNA vaccines; CARCINOEMBRYONIC antigen
- Publication
Gene Therapy, 2000, Vol 7, Issue 18, p1527
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301274