RRC ID 41677
Author Yamanaka R, Zullo SA, Ramsey J, Yajima N, Tsuchiya N, Tanaka R, Blaese M, Xanthopoulos KG.
Title Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus-mediated interleukin-12.
Journal J Neurosurg
Abstract OBJECT:The authors evaluated dendritic cell (DC)-based immunotherapy for malignant brain tumor to improve its therapeutic efficacy.
METHODS:Dendritic cells were isolated from bone marrow and pulsed with phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector GCsap-interleukin (IL)-12, and SFV-IL-12, respectively, to treat mice bearing brain tumors of the B16 cell line. The results indicated that therapeutic immunization with DCs pulsed with SFV-IL-12 prolonged the survival of mice with established tumors. Semliki Forest virus induced apoptosis in DCs, which in turn facilitated the uptake of apoptotic cells by other DCs, thus providing a potential mechanism for enhanced immunogenicity.
CONCLUSIONS:Therapy with DCs that have been pulsed with SFV-mediated IL-12 may be an excellent step in the development of new cancer vaccines. Intratumorally injected DCs that have been transiently transduced with IL-12 do not require pulsing of a source of tumor antigens to induce tumor regression.
Volume 97(3)
Pages 611-8
Published 2002-9-1
DOI 10.3171/jns.2002.97.3.0611
PMID 12296646
MeSH Animals Apoptosis / immunology Bone Marrow Cells Brain Neoplasms / immunology Brain Neoplasms / therapy* CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / immunology Dendritic Cells / immunology* Dendritic Cells / virology Genetic Therapy Genetic Vectors Glioma / immunology Glioma / therapy* Immunotherapy, Active Interferon-gamma / biosynthesis Interleukin-12 / genetics* Interleukin-12 / immunology* Mice Mice, Inbred C57BL Semliki forest virus / genetics* Transduction, Genetic Tumor Cells, Cultured / transplantation
IF 3.968
Times Cited 42
Human and Animal Cells B16