GROWTH-INHIBITION OF SUBCUTANEOUSLY TRANSPLANTED HUMAN GLIOMA BY TRANSFECTION-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA AND AUGMENTATION OF THE EFFECT BY GAMMA-INTERFERON

Using subcutaneous solid tumors produced by U251-MG human glioma cells , we studied the in vivo transfection of the cells with the tumor necr osis factor-alpha (TNF-alpha) gene delivered by means of liposomes. Wh en the tumor had become 7 mm in diameter, liposomes with entrapped TNF -alpha gene were injected into the center of the subcutaneous tumor. W e found that mRNA of transfection-induced TNF-alpha, which was express ed in the tumor tissue, was detected by reverse transcriptase-polymera se chain reaction (RT-PCR) method and its protein was demonstrated by enzyme-linked immunoassay. Growth of the tumor was inhibited when the injection was carried out five times at every other day. The growth-in hibitory effect by transfection-induced TNF-alpha was much remarkable as compared with exogenous TNF-alpha and the effect was enhanced by th e intraperitoneal injection of gamma-interferon (IFN-gamma) 12 h prior to intratumoral injection of the liposomes.