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设计包含肿瘤相关碳水化合物 Tn 抗原和脂氨基酸基 Toll 样受体 2 配体的完全合成、自佐剂疫苗。

Design of fully synthetic, self-adjuvanting vaccine incorporating the tumor-associated carbohydrate Tn antigen and lipoamino acid-based Toll-like receptor 2 ligand.

机构信息

School of Chemistry and Molecular Biosciences (SCMB), The University of Queensland , QLD 4072, Queensland, Australia.

出版信息

J Med Chem. 2012 Aug 9;55(15):6968-74. doi: 10.1021/jm300822g. Epub 2012 Jul 25.

Abstract

Overexpression of certain tumor-associated carbohydrate antigens (TACA) caused by malignant transformation offers promising targets to develop novel antitumor vaccines, provided the ability to break their inherent low immunogenicity and overcome the tolerance of the immune system. We designed, synthesized, and immunologically evaluated a number of fully synthetic new chimeric constructs incorporating a cluster of the most common TACA (known as Tn antigen) covalently attached to T-cell peptide epitopes derived from polio virus and ovalbumin and included a synthetic built-in adjuvant consisting of two 16-carbon lipoamino acids. Vaccine candidates were able to induce significantly strong antibody responses in mice without the need for any additional adjuvant, carrier protein, or special pharmaceutical preparation (e.g., liposomes). Vaccine constructs were assembled either in a linear or in a branched architecture, which demonstrated the intervening effects of the incorporation and arrangement of T-cell epitopes on antibody recognition.

摘要

某些肿瘤相关碳水化合物抗原(TACA)的过度表达是恶性转化的结果,为开发新型抗肿瘤疫苗提供了有希望的靶点,前提是能够打破其固有的低免疫原性并克服免疫系统的耐受。我们设计、合成并免疫评估了许多新型嵌合构建体,这些构建体包含一组最常见的 TACA(称为 Tn 抗原),通过共价键与来自脊髓灰质炎病毒和卵清蛋白的 T 细胞肽表位相连,并包含由两个 16 碳脂氨基组成的合成内置佐剂酸。疫苗候选物无需任何额外的佐剂、载体蛋白或特殊药物制剂(例如脂质体)即可在小鼠中诱导出显著强烈的抗体反应。疫苗构建体采用线性或分支结构组装,这证明了 T 细胞表位的掺入和排列对抗体识别的干预作用。

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