一、TNF的发现19世纪末,Bruns和Coley先后报导给某些肿瘤患者感染细菌或注射细菌毒素混合物后,肿瘤会缩小。此后,Coley等开始使用化脓链球菌(Streptococcus pyogenes)与灵杆菌(Serratia marcescens)的混合物治疗癌症。此混合物被人称为Coley’s毒素。美国医学协会于1934年宣布,Coley’s毒素是当时已知的全身性治疗癌症的唯一办法。以后,随着放射治疗、化学治疗等疗法的相继出现,Coley’s毒素在临床上逐渐被淘汰了。尽管如此,人们将微生物产物用于抗肿瘤的实验室研究却一直没有停止,并且有重要发现:注射革兰氏阴性细菌培养液的 First, the discovery of TNF The late 19th century, Bruns and Coley has reported to some cancer patients infected with bacteria or injection of bacterial toxins mixture, the tumor will shrink. Since then, Coley et al began to treat cancer using a mixture of Streptococcus pyogenes and Serratia marcescens. This mixture is called Coley’s toxin. The American Medical Association announced in 1934 that Coley’s toxin was the only known systemic treatment for cancer at the time. Later, with the radiotherapy, chemotherapy and other therapies have emerged, Coley’s toxin gradually eliminated in clinical. Nevertheless, laboratory studies on the use of microbial products for antitumor have not stopped, and important findings have been made: injection of Gram-negative bacterial cultures