新型基因工程人肿瘤坏死因子-α的临床前研究

Preclinical study of a novel recombinant human tumor necrosis factor-α

目的 研究一种新型基因工程人肿瘤坏死因子－α（ｎｒｈＴＮＦ－α）的临床前药理、毒理和药代动力学特性。方法观察ｎｒｈＴＮＦ－α对动物移植性肿瘤的抑制作用、毒副作用（如急性中毒反应和死亡情况，过敏反应，以及对神经系统、呼吸系统、心血管系统、造血系统和免疫系统的影响）及药代动力学变化。结果ｎｒｈＴＮＦ－α具有明显的抑瘤作用且呈剂量依赖性。对动物的急性中毒表现及病理变化与ｒｈＴＮＦ－α相似，未见其他不良反应。结论ｎｒｈＴＮＦ－α的抑瘤作用明显，毒副反应低，具有良好的临床应用前景。

Aim To study the preclinical pharmacology, toxicology and pharmacokinetics characteristics of a novel recombinant tumor necrosis factor-α(nrhTNF-α). MethodsThe observation was carried out on the inhibitory effect, toxic and adverse effects (including acute toxicosis reaction, mortality, allergy reaction, and the affections on nervous system, respiratory system, cardiovascular system, hemopoietic system and immune system), as well as the pharmacokinetics of nrhTNF-α on the animal transplanted tumors.Results nrhTNF-α can obviously inhibit tumors in a dose dependent manner. The acute toxic reaction and its pathology of nrhTNF-αare similar to those of rhTNF-α. Besides, there is no other adverse reaction observed. Conclusion nrhTNF-α has a very good tumor inhibitory function and low adverse reaction. Therefore, it has a prospect of clinical applications.