|Title:||CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination||Authors:||WEN-FANG CHENG
|Issue Date:||2003||Journal Volume:||10||Journal Issue:||16||Start page/Pages:||1311-1320||Source:||Gene Therapy||Abstract:||
One of the major hurdles facing cancer immunotherapy is that cancers may downregulate expression of MHC class I molecules. The development of a suitable tumor model with downregulated MHC class I expression is critical for designing vaccines and immunotherapeutic strategies to control such tumors. We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15). Using this model, we tested DNA and vaccinia vaccines for their ability to control tumors with downregulated MHC class I expression. We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect. Lymphocyte depletion experiments revealed that both-CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A 15). Furthermore, tumor protection experiments using IFN-γ knockout mice revealed that IFN-γ was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A 15). Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-γ in generating this antitumor effect.
|ISSN:||0969-7128||DOI:||10.1038/sj.gt.3301982||SDG/Keyword:||CD8 antigen; DNA vaccine; gamma interferon; heat shock protein 70; major histocompatibility antigen class 1; vaccinia vaccine; animal experiment; animal model; antineoplastic activity; cancer control; cancer immunotherapy; controlled study; down regulation; drug effect; female; gene expression regulation; genetic code; knockout mouse; lymphocyte depletion; mouse; Mycobacterium; natural killer cell; nonhuman; priority journal; review; T lymphocyte subpopulation; tumor cell line; tumor model; vaccination; Animals; CD8-Positive T-Lymphocytes; Cytokines; Female; Flow Cytometry; Gene Therapy; Genes, MHC Class I; Interferon Type II; Killer Cells, Natural; Lymphocyte Depletion; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Models, Animal; Neoplasms, Experimental; Vaccines, DNA; Animalia; Murinae; Mycobacterium
|Appears in Collections:||醫學系|
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