人MUC1和鼠Muc1蛋白疫苗抗肿瘤作用的比较

J4 ›› 2010, Vol. 36 ›› Issue (1): 114-118.

人MUC1和鼠Muc1蛋白疫苗抗肿瘤作用的比较

方芳|宋献美|张庆勇|马吉春|窦蕊|陈文博|台桂香

吉林大学基础医学院免疫学教研室|吉林长春 130021

收稿日期:2009-07-08 出版日期:2010-01-28 发布日期:2010-01-28
通讯作者: 台桂香(Tel：0431-85619403，E-mail：taiguixiang@163.com) E-mail:taiguixiang@163.com
作者简介:方芳（1973-）|女|吉林省吉林市人|在读医学博士|主要从事肿瘤疫苗的研究。 
基金资助:
吉林省科技厅科技发展计划项目资助课题（20080931）

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

FANG Fang, SONG Xian-Mei, ZHANG Qing-Yong, MA Ji-Chun, DOU Rui, CHEN Wen-Bo, Tai Gui-Xiang

Department of Immunology,School of Basic Medical Sciences,Jilin University,Changchun 130021,China

Received:2009-07-08 Online:2010-01-28 Published:2010-01-28

摘要/Abstract

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。

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

Abstract:

Abstract:Objective To study the anti-tumor effect of recombinant human MUC1-MBP and mouse Muc1-MBP protein vaccines,and provide the basis for clinical application of tumor vaccine.Methods The mice were divided three groups and respectively immunized with PBS (negative control),human MUC1-MBP and mouse Muc1-MBP fusion protein.The cross reaction between anti-human MUC1 and anti-mouse Muc1 antibody was detected by ELISA.CTL-specific 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 68.5%,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) mm3,respectively,in the animal models of human breast cancer. The masses of tumor were obviously suppressed in MUC1-MBP group (P<0.01) and Muc1-MBP group (P<0.05) compared with control group.Conclusion 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.

Key words: human MUC1-MBP;mouse Muc1-MBP;recombinant fusion proteins;cancer vaccine;cross reaction

中图分类号:

R730.5

方芳, 宋献美, 张庆勇, 马吉春, 窦蕊, 陈文博, 台桂香. 人MUC1和鼠Muc1蛋白疫苗抗肿瘤作用的比较[J]. J4, 2010, 36(1): 114-118.

FANG Fang, SONG Xian-Mei, ZHANG Qing-Yong, MA Ji-Chun, DOU Rui, CHEN Wen-Bo, Tai Gui-Xiang. Comparison of anti-tumor effect between human MUC1-MBP and mouse　Muc1-MBP |fusion protein vaccine[J]. J4, 2010, 36(1): 114-118.