Experimental Tumor Immunotherapy with TNF Gens Transduced Cells / 中国肿瘤生物治疗杂志

ABSTRACT

The tumor necrosis factor(TNF) secreted by gene modified tumor cells can lead to very effective tumor rejection. This effect of TNF on tumor growth is mediated mainly by the induction of an antitumor immune response. It requires a local and continuous presence of TNF at the tumor site. Tumor suppression induced by TNF is close dependent and a complete tumor eradication must not be accompanied by systemic toxic side effects. A complex pattern of tumor infiltrating cells has been observed in TNF producing tumors, consisting of macrophages, CD4+ and CD8~(+)T cells. For efficient tumor inhibition maccophages and CD8~(+)T cells are needed,whereas CD4~(+)T cells seem to be innocent bystander cells. TNF is also effective in T eell deficient mice, but in most cases for complete tumor elimination T ceils have to be present. Depending on the cell lines used or the levels of TNF secreted by transduced tumor cells, systemic toxicity of TNF has also been observed including cachexia or wasting of the experimental animals. In some cases, TNF gene transfected tumors did not show growth inhibition in vivo, but rather, their metastases were enhanced. Using TNF producing tumor cells as vaccine, no systemic protective immunity against a parental tumor cell challenge has been observed.