rhTNFα D11a对S180肉瘤的体内抗肿瘤作用

IN VIVO ANTITUMOR EFFECTS ON rhTNFα D11a TO S180 SARCOMA

ｒｈＴＮＦαＤ１１ａ是利用基因工程技术制备的一种新型ＴＮＦ。体外在极低浓度下对多种人源性和鼠源性肿瘤细胞均有明显的细胞毒作用，与原型ｒｈＴＮＦα相比，其活性高１０倍以上；在小鼠和猴子体内进行的急性毒性和慢性毒性试验表明：其毒性比原型ｒｈＴＮＦα低约７倍。本文研究了ｒｈＴＮＦαＤ１１ａ在荷瘤小鼠体内的抗肿瘤作用，结果表明：瘤内注射１×１０４Ｕ的ｒｈＴＮＦαＤ１１ａ，７０％的动物肿瘤完全消失，其余动物肿瘤极显著减小，且发生组织重度坏死；注射１×１０３Ｕ，１０％的动物肿瘤完全消失，９０％的肿瘤不同程度地减小，肿瘤组织坏死程度以轻、中度为主；注射１×１０２Ｕ的动物肿瘤无明显减小，但生长率均显著低于对照组。

rhTNFα D11a, a TNF mutant, was cytotoxical to a number of human and murine cancer cell lines in vitro in very low concentration. It was demonstrated that the rhTNFα D11as activity was 10 times larger than the wild rhTNFs.Its immediate and delayed toxicity on mouse and monkey was 1/7 of the wild. In this paper, we observed the antitumor effects on cancer tissue implanted into mice. 70% of the S180 derived cancer, when intratumor adminstered 1×10 4U, completely disappeared. Other 30% tumor showed the decrease in size and heavy necrosis; in the dose of 1×10 3U,10%tumor disappeared, other 90% decreased in size in different degree, mode rate or slight necrosis;1×10 2U in jection showed little effect on tumor size, however, its growth rate was significantly slower than the controls.