肿瘤坏死因子对淋巴激活素活化的杀伤细胞抗肿瘤活性的影响

THE EXPERIMENT STUDY OF THE ANTI-TUMOR EFFECT WITH TNF INDUCING LAK CELL

用B_(16)W_(10)黑色素瘤作靶瘤,C_(57)BL/6小鼠为荷瘤动物,小鼠脾细胞经白细胞间介质-2培养3d为效应细胞即LAK细胞,观察了肿瘤坏死因子对LAK细胞抗肿瘤活性的影响。体外实验结果表明:单独肿瘤坏死因子(500U/ml)或低剂量白细胞间介质-2(10U/ml)均不影响LAK细胞的杀瘤活性;肿瘤坏死因子能增强亚适剂量白细胞间介质-2(100U/ml)诱导的LAK细胞活性。而不增强最适剂量白细胞间介质-2(1000U/ml)诱导的LAK细胞活性。体内实验结果表明:对局部肿瘤,瘤内同时注射肿瘤坏死因子和白细胞间介质-2和LAK细胞时,6只荷瘤鼠4只瘤块消失。其中2只存活期超过60d。对全身肺转移癌、肿瘤坏死因子、白细胞间介质-2和LAK细胞联合静脉注射亦显抗瘤作用增强,该组小鼠肺表面瘤结节数和肺结节发生率减少。

B_(16)W_(10) melanoma was used as target cell. In vitro, 500 U/ml TNF in combination with varing doses of IL-2 were examined for their effect of LAK induction. TNF alone or low dose IL-2 (10 U/ml) was ineffective in inducing a lyric activity. The of- feet was notable only when TNF combined with suboptimal dose IL-2 (100 U / ml). No further effect was observed at optimal IL-2 (1 000 U/ml). In vivo, studies of the therapeutic antitumor effects of TNF and IL-2/LAK showed that they were very effective against B_(16) melanoma. Treatment of established B_(16) melanoma with intratumoral injection of rhTNF combining with IL-2/LAK cell caused 4 of 6 mice disappearance of tumor mass after the tenth days of the injection. 2 of 6 mice survied more than 60 days. Treatment effect on lung metastasis with iv injection of rTNF and IL-2/LAK was the best (P<0.05).