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首页> 外文期刊>Vaccine >Comparison of prophylactic and therapeutic immunisation with an ErbB-2 (HER2) fusion protein and immunoglobulin V-gene repertoire analysis in a transgenic mouse model of spontaneous breast cancer.
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Comparison of prophylactic and therapeutic immunisation with an ErbB-2 (HER2) fusion protein and immunoglobulin V-gene repertoire analysis in a transgenic mouse model of spontaneous breast cancer.

机译:在自发性乳腺癌的转基因小鼠模型中,使用ErbB-2(HER2)融合蛋白和免疫球蛋白V基因库分析进行预防性和治疗性免疫的比较。

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摘要

ErbB-2 is associated with several solid tumours of which breast cancer is the commonest cancer in women worldwide. Though anti-ErbB-2 antibody appears to play a significant role in prevention and therapy, naturally occurring anti-ErbB-2 antibody associated with the cleaved ectodomain of overexpressed ErbB-2 self antigen is detectable in patients. It is therefore essential to understand the course of antibody mediated protection during disease progression. 100% of FVB/Nneu mice expressing mutated, constitutively active ErbB-2 develop mammary carcinoma. It has been shown that vaccination with ErbB-2 associated with a T helper cell epitope P30 can offer protection against transplantable tumour but it is unclear whether the same vaccine protects against naturally developing tumour. We have analysed the course of the disease following prophylactic, and therapeutic vaccination in this spontaneous, eutopic mammary carcinoma model that more closely resembles the human disease. 100% protection against tumour development was observed subsequent to prophylactic immunisation but disease progression was unaffected by therapeutic vaccination. The antibody response exhibited restricted expansion of the Immunoglobulin (Ig) variable (V)-gene repertoire by ErbB-2 specific B cells compared with the non-antigen specific B cell pool and control mice. The serum antibody profile was similar in therapeutically injected mice without any effect on tumour burden.
机译:ErbB-2与几种实体瘤有关,其中乳腺癌是全世界女性中最常见的癌症。尽管抗ErbB-2抗体似乎在预防和治疗中起着重要作用,但在患者中仍可检测到与过量表达的ErbB-2自身抗原的切割胞外域相关的天然存在的抗ErbB-2抗体。因此,必须了解疾病进展过程中抗体介导的保护过程。表达突变的组成型活性ErbB-2的FVB / N neu 小鼠100%患上了乳癌。已经显示用与T辅助细胞表位P30相关的ErbB-2的疫苗接种可以提供针对可移植肿瘤的保护,但是尚不清楚相同的疫苗是否可以针对自然发展的肿瘤进行保护。我们已经在这种更接近人类疾病的自发,异位乳腺癌模型中分析了预防性和治疗性疫苗接种后的疾病进程。预防性免疫后,观察到针对肿瘤发展的100%保护,但疾病进展不受治疗性疫苗接种的影响。与非抗原特异性B细胞库和对照小鼠相比,抗体应答显示ErbB-2特异性B细胞限制了免疫球蛋白(Ig)可变(V)基因库的扩增。在治疗注射的小鼠中,血清抗体谱相似,对肿瘤负荷没有任何影响。

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