Gerspach Jeannette, Pfizenmaier Klaus, Wajant Harald
Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
Biofactors. 2009 Jul-Aug;35(4):364-72. doi: 10.1002/biof.50.
Tumor necrosis factor (TNF) is highly pleiotropic cytokine regulating diverse cellular processes such as proliferation, cell migration, angiogenesis, differentiation, apoptosis, necrosis, but also survival. Because of its name-giving tumor necrosis-inducing capabilities, TNF has attracted attention very early for antitumor therapy. Although TNF is in clinical use for treatment of soft tissue sarcoma in isolated limb perfusion, its broad use in tumor therapy is prevented so far by its strong systemic proinflammatory effects. Nevertheless, over the past decade, a variety of tailor-made TNF variants have been developed with the aim to reduce TNFs systemic activity without losing its antitumoral effects. Here, we review the progress made toward improving the efficacy of TNF by genetic engineering, tumor targeting, and introduction of prodrug concepts.
肿瘤坏死因子（TNF）是一种高度多效性的细胞因子，可调节多种细胞过程，如增殖、细胞迁移、血管生成、分化、凋亡、坏死，还包括细胞存活。由于其具有赋予名称的诱导肿瘤坏死的能力，TNF很早就引起了抗肿瘤治疗领域的关注。尽管TNF在临床中用于孤立肢体灌注治疗软组织肉瘤，但迄今为止，其在肿瘤治疗中的广泛应用因强烈的全身促炎作用而受到阻碍。然而，在过去十年中，人们开发了多种特制的TNF变体，旨在降低TNF的全身活性，同时不丧失其抗肿瘤作用。在此，我们综述了通过基因工程、肿瘤靶向和引入前药概念在提高TNF疗效方面所取得的进展。
