Effects of irradiated tumor vaccine and infusion of granulocyte-macrophage colony-stimulating factor and interleukin-12 on established gliomas in rats.
OBJECTIVE
We investigated granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) infused into the injection site of irradiated tumor vaccine (TV) as therapy for gliomas.


METHODS
Rats with subcutaneous RT-2 gliomas were treated with irradiated TV and/or subcutaneous infusion of GM-CSF and/or IL-12 via osmotic minipump 5 days after tumor-cell inoculation. Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activity were analyzed to investigate immune responses. Rats with intracerebral gliomas were treated with irradiated TV and infused GM-CSF/IL-12 3 days after tumor-cell inoculation. Tumor growth rates and animal survival were followed. Survivors were re-challenged with wild-type RT-2 cells subcutaneously or intracerebrally to study long-term anti-tumor immunity.


RESULTS
Rats with subcutaneous gliomas treated with GM-CSF and IL-12 or TV plus GM-CSF or IL-12 did not have increased survival rate (P>0.2), but did have prolonged survival time (P<0.05); in contrast, rats treated with TV plus GM-CSF/IL-12 had increased survival rate (P<0.05) and prolonged survival time (P<0.05) compared with controls. These treatment strategies showed enhanced CTL and NK cell activities. Rats with intra-cerebral gliomas treated with TV plus GM-CSF/IL-12 did not have increased survival rate (P=0.11), but did have prolonged survival time (P<0.0001). Survivors in each group were re-challenged with wild-type RT-2 cells, and all had long-term survival.


CONCLUSIONS
Irradiated TV plus continuous localized infusion of GM-CSF/IL-12 may induce a tumor-specific anti-tumor immune response on established subcutaneous or intra-cerebral gliomas, and such a treatment strategy deserves consideration as adjuvant treatment for glioma.
Chen
Jin-Cherng
JC
Department of Surgery, Buddhist Tzu Chi Dalin General Hospital, 2, Ming Shen Road, Dalin, Chia-Yi, Taiwan.
Chen
Yun
Y
Wu
Jiann-Ming
JM
Su
Yen-Hao
YH
Tai
Kuo-Feng
KF
Tseng
Sheng-Hong
SH
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000628:therapy; D019496:Cancer Vaccines / Q000528:radiation effects* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D040521:Subcutaneous Tissue; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor