Enhancement of antitumor immune response in glioma models in mice by genetically modified dendritic cells pulsed with Semliki forest virus-mediated complementary DNA.
OBJECTIVE
The aim of this study was to further investigate dendritic cell (DC)-based immunotherapy for malignant glioma to improve its therapeutic efficacy.


METHODS
Dendritic cells were isolated from the bone marrow and pulsed with phosphate-buffered saline, tumor RNA, tumor lysate, Semliki Forest virus (SFV)-LacZ, SFV-mediated B16 complementary (c)DNA, or SFV-mediated 203 glioma cDNA, respectively, to treat mice bearing tumors of the 203 glioma cell line. The results indicated that pre-immunization with DCs pulsed with the same type of cDNA as in the tumor by a self-replicating RNA vector (that is, SFV) protected mice from tumor challenge, and that therapeutic immunization prolonged the survival of mice with established tumors. The SFV induced apoptosis in DCs and their death 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 tumor cDNA may be an excellent procedure for the development of new cancer vaccines.
Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ryaman@pop11.odn.ne.jp
R
R
Yamanaka
S A
SA
Zullo
R
R
Tanaka
M
M
Blaese
K G
KG
Xanthopoulos
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018076:DNA, Complementary; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000401:mortality / Q000628:therapy*; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D012672:Semliki forest virus; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary