Human HER-2/neu protein immunization circumvents tolerance to rat neu: a vaccine strategy for 'self' tumour antigens.
Human HER-2/neu protein immunization circumvents tolerance to rat neu: a vaccine strategy for 'self' tumour antigens.
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人 HER-2/neu 蛋白免疫规避了对大鼠 neu 的耐受性：“自身”肿瘤抗原的疫苗策略。
DOI：
10.1046/j.1365-2567.1998.00424.x
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发表时间：
1998
期刊：
影响因子：
6.4
通讯作者：
Cheever,MA
中科院分区：
文献类型：
--
作者：
Disis,ML;Shiota,FM;Cheever,MA
许多新定义的肿瘤抗原是“自身”蛋白。由于对这些抗原的耐受性，对癌症患者进行免疫可能很困难。HER‐2/neu致癌蛋白就是这样一种“自身”肿瘤抗原。大鼠neu与人HER‐2/neu同源，为研究疫苗接种策略提供了模型系统。老鼠对新老鼠有耐受性。用这种“自身”蛋白接种疫苗不会引起可检测到的免疫反应。目前的研究评估了是否可以通过高度同源的外源人HER‐2/neu蛋白免疫来规避对大鼠neu的耐受性。用人HER‐2/neu胞内结构域（hICD）蛋白免疫大鼠，该蛋白与大鼠新ICD具有92%的同源性。用hICD免疫的动物产生了明显的抗体和T细胞反应，这些抗体和T细胞反应对人类HER - 2/neu和大鼠neu都具有特异性。新特异性抗体的滴度大于1:20 000。利用合成肽对抗体反应的特异性分析表明，该抗体对大鼠和人蛋白100%同源的表位具有实质性的反应性。检测到显著的T细胞反应（刺激指数>0）和大鼠新蛋白（刺激指数>4）。T细胞对人类和大鼠的ICD也有反应。结果表明，与“自身”肿瘤抗原高度同源的外源蛋白免疫可能是一种有效的“自身”肿瘤抗原疫苗策略。
Many newly defined tumour antigens are ‘self’ proteins. Immunizing cancer patients against these antigens may be difficult due to tolerance. The HER‐2/neu oncogenic protein is such a ‘self’ tumour antigen. Rat neu is homologous with human HER‐2/neu and provides a model system for studying vaccination strategies. Rats are tolerant to rat neu. Vaccination with this ‘self’ protein elicits no detectable immune response. The current studies evaluated whether tolerance to rat neu can be circumvented by immunizing with the highly homologous foreign human HER‐2/neu protein. Rats were immunized with human HER‐2/neu intracellular domain (hICD) protein that is 92% homologous to rat neu ICD. Animals immunized with hICD developed significant antibody and T‐cell responses that were specific for both human HER‐2/neu and rat neu. Neu‐specific antibodies were present in titres of greater than 1:200 000. Analysis of the specificity of the antibody response using synthetic peptides demonstrated substantial reactivity to an epitope with 100% homology between rat and human protein. Significant T‐cell responses (stimulation index>10) to hICD and rat neu protein (stimulation index>4) were detected. The T cells also responded to both human and rat ICD. The results imply that immunization with foreign proteins, which are highly homologous to ‘self’ tumour antigens, may be an effective vaccine strategy for ‘self’ tumour antigens.