Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus-mediated interleukin-12.
OBJECTIVE
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.
Yamanaka
Ryuya
R
Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ryaman@pop11.odn.ne.jp
Zullo
Susan A
SA
Ramsey
Jay
J
Yajima
Naoki
N
Tsuchiya
Naoto
N
Tanaka
Ryuichi
R
Blaese
Michael
M
Xanthopoulos
Kleanthis G
KG
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001854:Bone Marrow Cells; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012672:Semliki forest virus / Q000235:genetics*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000637:transplantation
D018664:Interleukin-12; D007371:Interferon-gamma