MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines
MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines
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DOI：
10.1007/pl00006677
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发表时间：
2000-01-01
影响因子：
5.8
通讯作者：
McKenzie, IFC
中科院分区：
文献类型：
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作者：
Acres, B;Apostolopoulos, V;McKenzie, IFC
用3种不同的MUC1疫苗免疫治疗剂免疫小鼠，分析MUC1特异性细胞毒性T细胞前体(CTLp)的频率。用含MUC1GST和甘露聚糖偶联的MUC1GST融合蛋白或同时表达MUC1GST和IL-2的重组痘苗病毒免疫小鼠。用这些疫苗观察到了小鼠品系在免疫反应方面的变化。我们构建了人MUC1基因的转基因小鼠，以研究MUC1免疫后的特异性免疫反应和自身免疫的风险。用MUC1免疫的转基因小鼠被观察到部分耐受，因为MUC1特异性抗体反应低于同基因非转基因小鼠。然而，观察到对所有三种疫苗的显著MUC1特异性CTLp反应，表明这些小鼠有能力克服T细胞对MUC1的耐受性，但B细胞的耐受性较小。组织学分析表明，没有证据表明对表达人类MUC1分子的细胞具有自身免疫力。这些结果表明，在不损害表达该抗原的正常组织的情况下，对癌症相关抗原产生免疫反应是可能的。
Analyses of MUC1-specific cytotoxic T cell precursor (CTLp) frequencies were performed in mice immunized with three different MUC1 vaccine immunotherapeutic agents. Mice were immunized with either a fusion protein comprising MUC1 and glutathione S-transferase (MUC1-GST), MUC1-GST fusion protein coupled to mannan (MFP) or with a recombinant vaccinia virus expressing both MUC1 and interleukin-2. Mouse strain variations in immune responsiveness have been observed with these vaccines. We have constructed mice transgenic for the human MUC1 gene to study MUC1-specific immune responses and the risk of auto-immunity following MUC1 immunization. Transgenic mice immunized with MUC1 were observed to be partially tolerant in that the MUC1-specific antibody response is lower than that observed in syngeneic but non-transgenic mice. However, a significant MUC1-specific CTLp response to all three vaccines was observed, indicating the ability to overcome T cell, but to a lesser extent B cell, tolerance to MUC1 in these mice. Histological analysis indicates no evidence of auto-immunity to the cells expressing the human MUC1 molecule. These results suggest that it is possible to generate an immune response to a cancer-related antigen without damage to normal tissues expressing the antigen.