Vaccination for experimental gliomas using GM-CSF-transduced glioma cells.
Brain tumors have an immunoprivileged status which contributes to their refractoriness to treatment. In this study, immune rejection of GL261 glioma tumors in the mouse brain was achieved by subcutaneous vaccination with GM-CSF-transduced glioma cells. Cultured GL261 cells were transduced to secrete murine GM-CSF using a retrovirus vector, then irradiated, and injected subcutaneously into H-2 matched C57BL/6 mice. In prevaccination studies, the median survival time (MST) of animals vaccinated with 5 x 10(4) or 5 x 10(5) GM-CSF-transduced cells 7 days prior to intracranial injection of 10(6) nontransduced, nonirradiated GL261 cells was significantly prolonged by 45-50% compared with animals vaccinated in parallel with nontransduced, irradiated glioma cells. In treatment of established gliomas, the MST of animals, which were treated subcutaneously with 5 X 10(6) irradiated GM-CSF-transduced cells 3 days after intracranial injection of 2 x 10(4) nontransduced cells, was prolonged significantly by 36% compared with animals treated with the same number of nontransduced, irradiated cells or to sham-treated animals. In prevaccination studies, histology of brain tumors 4 days after intracranial tumor cell injection revealed infiltrates of CD8+ lymphocytes and eosinophils, the latter exclusively in animals vaccinated with GM-CSF-transduced cells, Thus, subcutaneous injection of irradiated GM-CSF-transduced glioma cells can induce a potent immune response to intracranial gliomas both as a vaccination against subsequent intracranial glioma cell implantation and for treatment of established intracranial glioma.
Herrlinger
U
U
Neurology Service, Massachusetts General Hospital East, Charlestown 02129, USA.
Kramm
C M
CM
Johnston
K M
KM
Louis
D N
DN
Finkelstein
D
D
Reznikoff
G
G
Dranoff
G
G
Breakefield
X O
XO
Yu
J S
JS
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D019496:Cancer Vaccines; D002460:Cell Line; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae; D015996:Survival Rate; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor