ISCOM 型白血病瘤苗联合1-甲基色氨酸免疫治疗荷瘤小鼠疗效观察

目的：探讨免疫刺激复合物（ISCOM ）型白血病肿瘤疫苗（简称瘤苗）联合1-甲基色氨酸对荷瘤小鼠的治疗作用。方法皂苷溶液中加入脂肪酶蛋白（1 mg／mL ）7℃反应12 h ，加入80μL 脂类混合物溶液和5 mL 皂苷溶液（1 mg／mL ）制备ISCOM 型白血病瘤苗。 C57BL／6小鼠分为模型组、ISCOM 型白血病瘤苗组、1-甲基色氨酸组和联用组（ISCOM 型白血病瘤苗＋1-甲基色氨酸），小鼠注射 FBL-3细胞建立白血病荷瘤小鼠模型，模型组给予等量生理盐水，其余各组接受对应药物治疗4周后，记录体质量，NK 细胞、Mφ细胞和细胞毒 T 淋巴细胞（CTL）细胞杀伤活性、血清 IL-10和 IL-12表达水平。结果联用组瘤质量低于1-甲基色氨酸组和 ISCOM 型白血病瘤苗组（0．64±0．26）g vs ．（2．49±0．91）g ，P＜0．01；（0．64±0．26）g vs ．（1．28±0．73） g ，P＜0．05）]；联用组 M φ细胞杀伤活性显著高于1-甲基色氨酸组（55．69±13．69）％ vs ．（69．47±14．79）％，P＜0．01）]；联用组NK 细胞杀伤活性显著高于1-甲基色氨酸组（38．41±8．27）％ vs ．（67．22±12．74）％，P＜0．01]；联用组 CTL 细胞杀伤活性高于1-甲基色氨酸组和 ISCOM 型白血病瘤苗组（43．77±8．89）％ vs ．（69．68±11．44）％，P ＜0．01；（58．87±9．45）％ vs ．（69．68±11．44）％，P＜0．05）]；联用组 IL-10均显著低于1-甲基色氨酸组、ISCOM 型白血病瘤苗组（76．2±6．82）pg／L vs ．（98．3±13．4） pg／L ，P＜0．01；（76．2±6．82）pg／L vs ．（202．3±44．5）pg／L ，P＜0．01）]；联用组 IL-12高于1-甲基色氨酸组、ISCOM 型白血病瘤苗组（381．2±47．3）pg／L vs ．（332．1±30．2）pg／L ，P ＜0．05；（381．2±47．3）pg／L vs ．（291．2±17．3）pg ／L ，P＜0．01）。结论ISCOM 白血病瘤苗联合1-甲基色氨酸具有较佳的抗瘤活性，其机制可能是通过介导 IL-10和 IL-12的表达。

The treatment effect of ISCOM leukemia vaccine combination with 1-methyl tryptophan on tumor burden mice

Objective Investigated the treatment effect of ISCOM leukemia vaccine combination with 1-methyl tryptophan on tumor burden mice .Methods Saponin was added lipase protein (1 mg/mL) 7 ℃ for 12 h ,adding 80 μL lipid mixed solution and 5 mL saponin solution (1 mg/mL ) to prepare ISCOM leukemia vaccine .C57BL /6 mice were randomly divided into model group , ISCOM leukemia vaccine group ,1-methyl tryptophan group and combination group ,Mice were injected FBL-3 cell to built leukemia tumor-burdened mice model .After treatment for 4 weeks ,tumors weight ,NK and Mφ and CTL cell killing activity ,serum levels of IL-10 ,IL-12 were detected .Results Tumor weight in combination group was less than 1-methyl tryptophan and ISCOM leukemia group (0 .64 ± 0 .26)g vs .(2 .49 ± 0 .91)g ,P< 0 .01 ,(0 .64 ± 0 .26)g vs .(1 .28 ± 0 .73)g ,P< 0 .05] ;NK cell killing activity in com-bination group was higher than 1-methyl tryptophan group(38 .41 ± 8 .27)% vs .(67 .22 ± 12 .74)% ,all P< 0 .01)] ;M φ activity in combination group was significantly higher than 1-methyl tryptophan group(55 .69 ± 13 .69)% vs .(69 .47 ± 14 .79)% ,P< 0 .01] ;CTL activity in combination group was significantly higher than 1-methyl tryptophan group and ISCOM leukemia group(43 .77 ± 8 .89)% vs .(69 .68 ± 11 .44)% ,P< 0 .01 ,(58 .87 ± 9 .45)% vs .(69 .68 ± 11 .44)% ,P < 0 .05] ;IL-10 in combination group were significantly lower than 1 - methyl tryptophan group and ISCOM leukemia group (76 .2 ± 6 .82)pg /L vs .(98 .3 ± 13 .4)pg/L ,P<0 .01 ,(76 .2 ± 6 .82)pg/L vs .(202 .3 ± 44 .5)pg/L ,P < 0 .01] ;IL-12 in combination group were significantly higher than 1-methyl tryptophan group and ISCOM leukemia group(381 .2 ± 47 .3)pg/L vs .(332 .1 ± 30 .2)pg/L ,P < 0 .05 ,(381 .2 ± 47 .3)pg /L vs . (291 .2 ± 17 .3)pg/L ,P< 0 .01] .Conclusion Combination with 1-methyl tryptophan and ISCOM leukemia vaccine has a well anti-tumor effect ,its mechanism may be through mediated and the expression of IL-12 and IL-10 .