Induction of a therapeutic antitumor immunological response by intratumoral injection of genetically engineered Semliki Forest virus to produce interleukin-12.
OBJECTIVE
The authors investigated immunogene therapy for malignant glioma to determine whether its therapeutic efficacy could be improved.


METHODS
Four groups of 203-glioma-bearing mice were treated with injections of phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector DFG-interleukin (IL)-12, and SFV-IL12, respectively. The results indicated that therapeutic immunization with SFV-IL12 prolonged the survival of mice with established tumors. Semliki Forest virus induces apoptotic death to glioma cells, which facilitates the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity.


CONCLUSIONS
Immunogene therapy with IL-12 via SFV may be an excellent candidate for the development of new cancer vaccines.
Yamanaka
R
R
Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ryaman@pop11.odn.ne.jp
Zullo
S A
SA
Tanaka
R
R
Ramsey
J
J
Blaese
M
M
Xanthopoulos
K G
KG
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics*; D007668:Kidney / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000235:genetics; D012672:Semliki forest virus / Q000235:genetics*; D015996:Survival Rate; D014162:Transfection
D011994:Recombinant Proteins; D018664:Interleukin-12