Synthesis and immunological evaluation of self-assembling and self-adjuvanting tricomponent glycopeptide cancer-vaccine candidates.
Synthesis and immunological evaluation of self-assembling and self-adjuvanting tricomponent glycopeptide cancer-vaccine candidates.
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DOI：
10.1002/chem.201202629
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发表时间：
2012-12
期刊：
影响因子：
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通讯作者：
Brendan L Wilkinson;Stephanie L Day;R. Chapman;S. Perrier;V. Apostolopoulos;R. Payne
中科院分区：
文献类型：
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作者：
Brendan L Wilkinson;Stephanie L Day;R. Chapman;S. Perrier;V. Apostolopoulos;R. Payne
制备了自佐剂三组分疫苗，并在小鼠模型中对其自组装和免疫活性进行了评估。每种疫苗由一种肽或糖肽抗原组成，该抗原对应于肿瘤相关粘蛋白1 （MUC1）糖蛋白的可变数串联重复（VNTR）的完整拷贝、通用t细胞辅助肽表位PADRE和免疫佐剂Pam(3)CysSer。研究表明，疫苗可在水中自发自组装，形成大小从17纳米到25纳米不等的各向同性颗粒，并在不添加外部佐剂的情况下在小鼠模型中引起强烈的体液反应。血清抗体可以识别MCF7乳腺癌细胞和B16黑色素瘤细胞表面的肿瘤相关MUC1表位，这些表位过表达这种肿瘤相关糖蛋白。
Self-adjuvanting tricomponent vaccines were prepared and assessed for their self-assembly and immunological activity in mouse models. The vaccines each consisted of a peptide or glycopeptide antigen that corresponds to a complete copy of the variable-number tandem repeat (VNTR) of the tumor-associated mucin 1 (MUC1) glycoprotein, the universal T-cell helper peptide epitope PADRE, and the immunoadjuvant Pam(3)CysSer. The vaccines were shown to spontaneously self-assemble in water to form isotropic particles varying in size from 17 to 25 nm and elicited robust humoral responses in murine models without the addition of an external adjuvant. The serum antibodies could recognize tumor-associated MUC1 epitopes on the surface of MCF7 breast-cancer cells and B16 melanoma cells, which overexpress this tumor-associated glycoprotein.