Vaccine therapy with dendritic cells transfected with Il13ra2 mRNA for glioma in mice.
OBJECTIVE
The Il13ra2 gene is often overexpressed in brain tumors, making Il13ra2 one of the vaccine targets for immunotherapy of glioma. In this study, using a mouse glioma model, the authors tested the hypothesis that vaccination using dendritic cells transfected with Il13ra2 mRNA induces strong immunological antitumor effects.


METHODS
A plasmid was constructed for transduction of the mRNAs transcribed in vitro into dendritic cells. This was done to transport the intracellular protein efficiently into major histocompatibility complex class II compartments by adding a late endosomal/lysosomal sorting signal to the Il13ra2 gene. The dendritic cells transfected with this Il13ra2 mRNA were injected intraperitoneally into the mouse glioma model at 3 and 10 days after tumor cell implantation. The antitumor effects were estimated based on the survival rate, results of histological analysis, and immunohistochemical findings for immune cells.


RESULTS
The group treated by vaccination therapy with dendritic cells transfected with Il13ra2 mRNA survived significantly longer than did the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing CD4+ and CD8+ T cells were found in the group vaccinated with dendritic cells transfected with Il13ra2 mRNA.


CONCLUSIONS
These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with Il13ra2 mRNA for the treatment of malignant glioma.
Saka
Makoto
M
Department of Neurosurgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Amano
Takayuki
T
Kajiwara
Koji
K
Yoshikawa
Koichi
K
Ideguchi
Makoto
M
Nomura
Sadahiro
S
Fujisawa
Hirosuke
H
Kato
Shoichi
S
Fujii
Masami
M
Ueno
Koji
K
Hinoda
Yuji
Y
Suzuki
Michiyasu
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016130:Immunophenotyping; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000494:pharmacology; D012333:RNA, Messenger / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D014162:Transfection
D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D053663:Interleukin-13 Receptor alpha2 Subunit; D012333:RNA, Messenger; D002738:Chloroquine