Tobacco mosaic virus as a new carrier for tumor associated carbohydrate antigens.
Tobacco mosaic virus as a new carrier for tumor associated carbohydrate antigens.
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DOI：
10.1021/bc300244a
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发表时间：
2012-08-15
影响因子：
4.7
通讯作者：
Huang, Xuefei
中科院分区：
文献类型：
--
作者：
Yin, Zhaojun;Huong Giang Nguyen;Chowdhury, Sudipa;Bentley, Philip;Bruckman, Michael A.;Miermont, Adeline;Gildersleeve, Jeffrey C.;Wang, Qian;Huang, Xuefei
肿瘤相关碳水化合物抗原（TACA）作为抗肿瘤疫苗开发的靶点正在积极研究中。一个严重的挑战是这些抗原的低免疫原性。在这里，我们报告的结果上使用烟草花叶病毒（TMV）衣壳作为一个有前途的载体的弱免疫原性TACA，单体Tn抗原。铜（I）催化的叠氮化物-炔环加成反应在将Tn共价连接到TMV衣壳上方面是高度有效的，而无需求助于大量过量的Tn抗原。Tn附着的位置被证明是重要的。在TMV的N末端引入Tn是免疫沉默的，而附着到酪氨酸139引起强烈的免疫应答。通过酶联免疫吸附测定和聚糖微阵列筛选研究确定产生Tn特异性IgG和IgM抗体。高滴度IgG抗体的产生表明TMV平台含有辅助T细胞的必需表位，并且能够诱导抗体同种型转换。抗体对在其天然环境中展示的Tn抗原表现出强反应性，即，癌细胞表面，从而凸显了TMV作为有前途的TACA载体的潜力。
Tumor associated carbohydrate antigens (TACAs) are being actively studied as targets for anti-tumor vaccine development. One serious challenge was the low immunogenecity of these antigens. Herein, we report the results on using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide-alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities towards Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier.
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