|Title:||Naked RNA vaccine controls tumors with down-regulated MHC class I expression through NK cells and perforin-dependent pathways||Authors:||WEN-FANG CHENG
|Issue Date:||2004||Journal Volume:||34||Journal Issue:||7||Start page/Pages:||1892-1900||Source:||European Journal of Immunology||Abstract:||
One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of vaccines and immunotherapeutic strategies to control such tumors. A naked Sind-bis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA vaccine controls MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon vaccines. ? 2004 WILEY-VCH Verlag GmbH & Co. KGaA.
|ISSN:||0014-2980||DOI:||10.1002/eji.200424877||SDG/Keyword:||cancer vaccine; major histocompatibility antigen class 1; monoclonal antibody; perforin; polyinosinic polycytidylic acid; virus protein; virus vector; cancer vaccine; HLA antigen class 1; lymphokine; membrane protein; perforin; polyinosinic polycytidylic acid; pore forming cytotoxic protein; RNA; animal cell; animal experiment; animal model; antigen expression; antineoplastic activity; article; cancer cell culture; cancer control; cancer immunotherapy; controlled study; down regulation; drug design; female; growth inhibition; Herpes simplex virus 1; in vivo study; lymphocyte subpopulation; mouse; natural killer cell; nonhuman; priority journal; replicon; Sindbis virus; tumor cell; tumor growth; adoptive transfer; animal; C57BL mouse; cytology; cytotoxic T lymphocyte; down regulation; drug effect; genetics; immunology; lymphocyte count; metabolism; natural killer cell; neoplasm; pathology; transplantation; vaccination; Adoptive Transfer; Animals; Cancer Vaccines; Down-Regulation; Female; Histocompatibility Antigens Class I; Killer Cells, Natural; Lymphocyte Count; Lymphocyte Subsets; Lymphokines; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Neoplasms; Poly I-C; Pore Forming Cytotoxic Proteins; RNA; T-Lymphocytes, Cytotoxic; Vaccination
|Appears in Collections:||醫學系|
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