人MUC1和鼠Muc1蛋白疫苗抗肿瘤作用的比较  

Comparison of anti-tumor effect between human MUC1-MBP and mouse Muc1-MBP fusion protein vaccine

作　　者：方芳[1] 宋献美[1] 张庆勇[1] 马吉春[1] 窦蕊[1] 陈文博[1] 台桂香[1] 

机构地区：[1]吉林大学基础医学院免疫学教研室,吉林长春130021

出　　处：《吉林大学学报（医学版）》2010年第1期114-118,F0003,共6页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅科技发展计划项目资助课题(20080931)

摘　　要：目的:探讨重组人MUC1-MBP和鼠Muc1-MBP疫苗的抗肿瘤作用,为肿瘤疫苗的临床应用提供实验依据。方法:用人MUC1-MBP和鼠Muc1-MBP融合蛋白分别免疫小鼠,实验分为阴性对照组、人MUC1-MBP组和鼠Muc1-MBP组,ELISA方法分别检测小鼠血清抗人MUC1抗体与抗鼠Muc1抗体的交叉反应;LDH法检测小鼠抗人MUC1和鼠Muc1特异的CTL活性。通过小鼠肺癌转移模型及皮下人乳腺癌移植瘤模型检测人MUC1-MBP和鼠Muc1-MBP免疫诱导的抗肿瘤作用。结果:抗人MUC1抗体和鼠Muc1抗原可产生较强的交叉反应,抗鼠Muc1抗体与人MUC1抗原可产生较弱的交叉反应;人MUC1-MBP和鼠Muc1-MBP免疫均可诱导CTL杀伤活性,对MCF-7细胞杀伤活性分别为(48.7±7.1)%和(54.6±7.8)%,对LLC1细胞杀伤活性分别为(61.9±10.2)%和(43.5±8.4)%。人MUC1-MBP组和鼠Muc1-MBP组小鼠Lewis肺癌的肺结节转移抑制率分别为94.4%和68.5%;在人乳腺癌移植瘤实验中,人MUC1-MBP组、鼠Muc1-MBP组和PBS组小鼠肿瘤平均体积分别(23.5±15.7)、(56.5±46.7)和(142.8±70.2)mm3,人MUC1-MBP组和鼠Muc1-MBP组肿瘤体积明显小于对照组(P<0.01或P<0.05)。结论:人MUC1和鼠Muc1有共同的B和T细胞表位,人MUC1诱导的交叉反应更强烈;人MUC1-MBP诱导的抗肿瘤活性强于鼠Muc1-MBP抗肿瘤活性;人MUC1-MBP有希望发展成人类抗肿瘤疫苗。Objective To study the anti-tumor effect of recombinant human MUC1-MBP and mouse Muc1-MBP protein vaccines, and provide the basis for c1inical application of tumor vaccine. Methods The mice were divided three groups and respectively immunized with PBS （negative control）, human MUC1-MBP and mouse Muel-MBP fusion protein. The cross reaction between anti-human MUC1 and anti-mouse Muc1 antibody was detected by ELISA. CTL-specifie cytotoxicities of mice induced by MUC1 and Muc1 were detected by LDH. The anti-tumor effects of human MUC1 and mouse Muc1 were observed by establishing mice models of the lung cancer metastasis and the subcutaneous human breast cancer. Results The cross reaction between the antibody of human MUC1 and the antigen of mouse Muc1 was stronger than that between the antibody of mouse Muc1 and antigen of human MUC1. The cytotoxicities of CTL from immunized mice by human MUC1-MBP and mouse Muc1-MBP to the MCF- 7 cells were （48.7±7.1）% and （54.6±7.8）% or to LLC1 cells were （61.9 ±10.2）% and （43.5±8.4）%, respectively. The inhibitory rates of lung tumor nodules of Lewis lung cancer in human MUC1-MBP and mouse Muc1-MBP groups were 94.4% and 68.5G, respectively. The average tumor volumes in human MUC1-MBP,mouse Muc1-MBP and PBS groups were （23.5±15. 7）, （56.5±46. 7） and （142.8±70. 2） mm^2 , respectively, in the animal models of human breast cancer. The masses of tumor were obviously suppressed in MUC1-MBP group （P〈0.01） and Muei MBP group （P〈0.05） compared with control group. Conc1usion Human MUC1 and mouse Muc1 have common epitope of B and T cell and the human MUC1 could induce the stronger cross reaction. Human MUC1-MBP has significant anti-tumor effects than that of mouse Muc1-MBP, and it might be used to develop the protein vaccine against human carcinoma.

关 键 词：人MUC1-MBP 鼠Muc1—MBP 重组融合蛋白质类 癌症疫苗 交叉反应 

分 类 号：R730.5[医药卫生—肿瘤]