白血病肿瘤疫苗联合1-甲基色氨酸免疫治疗荷瘤小鼠疗效观察

Efficacy of leukemia vaccine combined 1-MT immune treatment of tumor-bearing mice

目的探讨白血病肿瘤疫苗（简称瘤苗）主动免疫治疗及联合吲哚2，3双加氧酶（IDO）的抑制剂1-甲基色氨酸（1-MT），在白血病荷瘤小鼠治疗中的作用。方法采用FBL-3细胞皮下注射建立荷瘤白血病小鼠模型；实验分为5组：正常对照组、PBS对照组、环磷酰胺（CTX）化疗组、单用瘤苗治疗组和瘤苗联合1-MT治疗组；观察各组小鼠的一般状况、肿瘤缓解率、肿瘤大小、转移情况及生存期。结果PBS对照组小鼠活动迟缓，体质量（含瘤结节质量）比其余各组均高；单用瘤苗组和瘤苗联合1-MT组小鼠活动、进食正常，体质量与正常小鼠差异不大；化疗组体质量明显减轻，出现脱毛、弓背、活动减少等，差异有统计学意义（F=57．71，P=000）；单用瘤苗组和瘤苗联合1-MT组治疗相关死亡率明显低于化疗组（0，0，40％）。瘤苗联合1-MT组完全缓解率与单用瘤苗组（61．1％、70．0％）比较，差异无统计学意义（X^2=0．221，P〉0．05），但瘤苗联合1-MT组的复发率低于单用瘤苗组（0，36．36％）；复发小鼠再应用1-MT，能明显抑制瘤结节的生长。单用瘤苗组和瘤苗联合1-MT组小鼠中位存活期明显高于化疗组和PBS对照组（X^2=52．13，P〈0．01）。各组小鼠整体瘤结节的变化比较差异有统计学意义（F=89．966，P=0．000）。结论白血病瘤苗在动物实验具有肯定的疗效，能明显抑制肿瘤的生长，延长小鼠生存时间，且副作用小。免疫治疗联合1-MT对白血病进行治疗，可以显著减少肿瘤的复发率；而免疫治疗有效后复发时应用1-MT，可以显著抑制肿瘤的生长。

Objective To explore the active immunotherapeutic effects of whole-cell leukemia vaccine combined with 1-methyl-tryptophan （1-MT, inhibitor of idoleamine 2,3-dioxygenase, IDO） treatment on leukemia. Methods The tumor-bearing mice model was made by hypodermic injection of FBL-3 cells. Then these mice were divided into 5 groups, normal group, PBS control group, CTX chemotherapy group, vaccine treated group and vaccine combined with 1-MT treated group （1-MT group）, respectively. The main outcome measures including general condition, response rate, tumor size, metastasis and survival time were investigated. Results The mice of PBS control group were slow to move and much heavier （including tumor nodules） than the other groups. No obvious difference was observed in activity, eating behavior and weight between normal group, vaccine treated group and 1-MT treated group. The mice of CTX chemotherapy group were observed epilation, arched body and worn, and those weights decreased significantly compared with other group. The treatment-related mortality of vaccine-treated group and 1-MT group was lower than that of CTX chemotherapy group significantly （0, 0 vs 40 %）. There were no significant difference in complete remission rates between vaccine treated group and 1-MT group （61.1% vs 70.0 %, X^2 = 0.221, P 〉0.05）. But the recurrence rate of 1-MT group was lower than vaccine treated group （0 vs 36.36 %）. The tumor nodules growth of recurrent mice could be inhibited by 1-MT. The mean survival time of vaccine treated group and 1-MT group were longer than that in CTX chemotherapy group and PBS control group （X^2 = 52.13, P 〈0.01）. Conclusion Whole-cell leukemia vaccine can inhibit tumor growth and prolong tumor-bearing mice survival time with remarkable curative effects and few side effects. Vaccine combined with 1-MT treatment can significantly reduce tumor recurrence rate, and 1-MT was still effective in inhibiting recurrence of tumor nodules growth after vaccine treatment.