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.
Smilowitz
H M
HM
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA. smilowitz@nso1.uchc.edu
Coderre
J A
JA
Nawrocky
M M
MM
Tu
W
W
Pinkerton
A
A
Jahng
G H
GH
Gebbers
N
N
Slatkin
D N
DN
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