Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA.
Rat C6 glioma cells express insulin-like growth factor I (IGF-I) and form rapidly growing tumors in syngeneic animals. When transfected with an episome-based vector encoding antisense IGF-I complementary DNA, these cells lost tumorigenicity. Subcutaneous injection of IGF-I antisense-transfected C6 cells into rats prevented formation of both subcutaneous tumors and brain tumors induced by nontransfected C6 cells. The antisense-transfected cells also caused regression of established brain glioblastomas when injected at a point distal to the tumor. These antitumor effects result from a glioma-specific immune response involving CD8+ lymphocytes. Antisense blocking of IGF-I expression may reverse a phenotype that allows C6 glioma cells to evade the immune system.
Trojan
J
J
INSERM, Paris.
Johnson
T R
TR
Rudin
S D
SD
Ilan
J
J
Tykocinski
M L
ML
Ilan
J
J
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D016827:CD8 Antigens / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004274:DNA, Recombinant; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D016372:RNA, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016827:CD8 Antigens; D004274:DNA, Recombinant; D016372:RNA, Antisense; D007334:Insulin-Like Growth Factor I