RRC ID 1958
Author Yamanaka R, Xanthopoulos KG.
Title Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18.
Journal DNA Cell Biol.
Abstract We constructed pSin-SV40-HDV-SV40pA, an improved Sindbis DNA expression vector, and evaluated the potential of this vector system for brain tumor therapy. We investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and mouse IL-18 would enhance the antitumor responses. To study the immune mechanisms involved in tumor regression, we examined tumor growth in B16-gp100-implanted brain tumor models using T-cell subset-depleted and IFN-gamma-neutralized mice. Hugp100/mIL-18 vaccination was also investigated for its antitumor effects against the wild-type murine B16 tumor, which expresses the murine gp100 molecule. Genetic immunization using plasmid pSin 9001 DNA codelivery of human gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on the malignant brain tumors. The antitumor and protective effects were mediated by both CD4(+)/CD8(+) T cells and IFN-gamma. Vaccination with hugp100/mIL-18 conferred a significant survival merit to wild-type B16 tumor-harboring mice. Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic gp100 and syngeneic IL-18 may be an excellent approach for developing a new treatment protocol. Thus, the Sindbis DNA system may represent a novel approach for the treatment of malignant brain tumors.
Volume 24(5)
Pages 317-24
Published 2005-5
DOI 10.1089/dna.2005.24.317
PMID 15869409
MeSH Animals Antigens, Neoplasm / genetics* Antigens, Neoplasm / immunology Brain Neoplasms / immunology Brain Neoplasms / therapy* Brain Neoplasms / virology CD4-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / immunology Cancer Vaccines / immunology Cancer Vaccines / therapeutic use* Cytotoxicity Tests, Immunologic DNA, Neoplasm / therapeutic use DNA, Viral / genetics Disease Models, Animal Genetic Therapy / methods* Genetic Vectors / administration & dosage Genetic Vectors / genetics Glioma / immunology Glioma / therapy Glioma / virology Humans Immunotherapy Injections, Intramuscular Interferon-gamma / biosynthesis Interleukin-18 / genetics Interleukin-18 / immunology Interleukin-18 / therapeutic use* Melanoma, Experimental / immunology Melanoma, Experimental / therapy Membrane Glycoproteins / immunology Membrane Glycoproteins / therapeutic use* Mice Mice, Inbred C57BL Mice, Knockout Neoplasm Proteins / immunology Neoplasm Proteins / therapeutic use* Neoplasm Transplantation Sindbis Virus / genetics Vaccination / methods Vaccines, DNA / therapeutic use gp100 Melanoma Antigen
IF 2.918
Times Cited 16
Human and Animal Cells B16 melanoma 4A5