The combination of X-ray-mediated radiosurgery and gene-mediated immunoprophylaxis for advanced intracerebral gliosarcomas in rats.
Rats with advanced, imminently lethal, approximately 4 mm diameter, left-sided intracerebral 9L gliosarcoma (9LGS), a well characterized malignant tumor with some similarities to human high-grade astrocytomas, were used as a therapy model 14 days post-implantation of 10(4) cells. Such tumor-bearing rats die within two weeks (median, 6 days) thereafter if untreated. However, if these tumors are exposed on day 14 to 12-25 Gy of an electron-equilibrated 6 MV photon beam (radiosurgery), survival is extended about 5-6 fold to a median of 34 days, but long-term survival (> 1 year) is increased only to approximately 18%. Multiple subcutaneous inoculations of radiation-disabled 9LGS cells post-radiosurgery (immunoprophylaxis) extended lifespan and long-term (> 1 year) survival minimally (median, 37 days; 25%, respectively). In sharp contrast, radiosurgery followed by multiple subcutaneous inoculations of radiation-disabled 9LGS cells that had been transfected with granulocyte macrophage colony stimulating factor (GMCSF), a cytokine with demonstrated immune-enhancing properties (i.e. gene-mediated immunoprophylaxis, GMIMPR) increased long-term survival to approximately 67%. To our knowledge, these results are the first to show that the combination of photon radiosurgery and GMIMPR is effective for an advanced, imminently lethal brain tumor in a mammal. These data raise the possibility that GMIMPR following radiation therapy might prove effective for the treatment of some human malignant gliomas.
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA. smilowitz@nso1.uchc.edu
H M
HM
Smilowitz
J A
JA
Coderre
M M
MM
Nawrocky
W
W
Tu
A
A
Pinkerton
G H
GH
Jahng
N
N
Gebbers
D N
DN
Slatkin
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D018316:Gliosarcoma / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D007167:Immunotherapy; D008279:Magnetic Resonance Imaging; D016634:Radiosurgery; D051381:Rats; D015996:Survival Rate; D014162:Transfection
D016178:Granulocyte-Macrophage Colony-Stimulating Factor