Chouaib S, Robinet E, Zyad A, Branellec D
Laboratoire d'immunologie URA-1156 CNRS, Institut Gustave-Roussy, Villejuif, France.
Bull Cancer. 1992;79(10):935-49.
Originally described for its capacity to induce hemorrhagic necrosis of transplantable tumors in mice, TNF-alpha also exerts cytotoxic effects against some tumor cell lines in vitro. It is now known that TNF is an essential mediator of cellular immunity and a wide variety of biological activities of TNF in vitro and in vivo has been reported. TNF is an important mediator of inflammation and is involved during the pathogenesis of several auto-immune, infectious or cancer diseases. While some immunomodulatory properties of TNF have at least been partially elucidated, the biochemical basis of TNF cytotoxic action remains largely unknown. Furthermore, the molecular mechanisms of TNF susceptibility have yet to be clarified. Clinical studies with recombinant TNF as an anticancer agent are encouraging. Multiple phase I and phase II trials have been carried out without major therapeutic effect. In fact, TNF resistance and TNF-induced systemic toxicity are two major limitations for the use of TNF as an antineoplastic agent. The clinical application of human TNF remains an area of active research and innovative approaches such as gene therapy need to be elaborated. The elucidation of the process of lysis and the modulation of TNF resistance are crucial to the future development of TNF and its use in antitumor therapy.
最初因其能诱导小鼠可移植肿瘤发生出血性坏死的能力而被描述，肿瘤坏死因子-α（TNF-α）在体外对某些肿瘤细胞系也具有细胞毒性作用。现在已知TNF是细胞免疫的重要介质，并且已经报道了TNF在体外和体内的多种生物学活性。TNF是炎症的重要介质，参与多种自身免疫性、感染性或癌症疾病的发病过程。虽然TNF的一些免疫调节特性至少已得到部分阐明，但其细胞毒性作用的生化基础仍 largely unknown。此外，TNF敏感性的分子机制尚未阐明。以重组TNF作为抗癌药物的临床研究令人鼓舞。已经进行了多项I期和II期试验，但没有显著的治疗效果。事实上，TNF耐药性和TNF诱导的全身毒性是将TNF用作抗肿瘤药物的两个主要限制。人TNF的临床应用仍是一个活跃的研究领域，需要详细阐述诸如基因治疗等创新方法。阐明裂解过程和调节TNF耐药性对于TNF的未来发展及其在抗肿瘤治疗中的应用至关重要。
