Observations with tumour necrosis factor gene-transfected tumours

Tumour necrosis factor (TNF) produced by genetically engineered tumour cells can lead to very effective tumour rejection. Tumour suppression does not result from a direct effect of TNF on tumour cells but rather is mediated by the induction of an anti-tumour immune response. It requires a local and continuous presence of TNF at the tumour site. Tumour rejection induced by TNF is dose-dependent and even tumour cell-derived TNF in amounts which cause complete tumour eradication must not be accompanied by toxic side effects. A complex pattern of tumour infiltrating cells has been observed in TNF-producing tumours consisting of macrophages, CD4+ and CD8+ T cells. For tumour suppression macrophages and CD8+ T cells are needed whereas CD4+ T cells seem to reflect innocent bystander cells. Consistently, TNF is active in T cell deficient mice but in most cases T cells are needed for complete tumour elimination. TNF was active in a number of different tumour models but recent experiments also showed that local TNF failed to induce an anti-tumour response in certain tumour models. Moreover, either depending on the tumour cell line used or on the level of TNF secreted by the tumour, systemic toxicity has been observed, leading to cachexia or wasting of the mice. In one case it has been shown that a TNF gene-transfected tumour showed no tumour growth inhibition in vivo but that TNF augmented metastasis of these cells. Experiments conducted to demonstrate systemic protective immunity by TNF-producing tumours used as a vaccine have not yet been successful.