Antitumor Activity of Recombinant Human Tumor Necrosis Factor-α (rH-TNFα) and Liposome-entrapped rH-TNFα

Abstract

The antitumor activities of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha were evaluated in various glioma cell lines and a rat brain T9 gliosarcoma model. rH-TNF alpha had a direct cytotoxic activity against various glioma cell lines in vitro, and indirect cytotoxic activity against gliosarcoma (T9) in vivo. Liposome-entrapped rH-TNF alpha had increased direct cytotoxic activity in vitro, and against experimentally induced brain tumors in vivo. The effects in vivo were probably due to vascular damage of the tumor vessels as shown by histological examination and activation of cytotoxic macrophages as shown in vitro. These results indicate that the general or local administration of liposome-entrapped rH-TNF alpha may become a useful adjunct treatment for malignant brain tumor.

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth

“…We therefore investigated the effect of TNFα on the survival of GSC-enriched and -depleted cultures. TNFα increased apoptosis in non-stem glioma cells (Figure 6A and 6B), consistent with prior results in glioma cell lines [70],[71]. In contrast, GSCs isolated from multiple human glioma xenografts were resistant to TNFα-induced cell death (Figure 6A and 6B and unpublished data).…”