L-Rhamnose Enhances the Immunogenicity of Melanoma-Associated Antigen A3 for Stimulating Antitumor Immune Responses.
L-Rhamnose Enhances the Immunogenicity of Melanoma-Associated Antigen A3 for Stimulating Antitumor Immune Responses.
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DOI：
10.1021/acs.bioconjchem.6b00081
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发表时间：
2016-03
影响因子：
4.7
通讯作者：
Huajie Zhang;Bin Wang;Zhongrui Ma;Mohui Wei;Jun O. Liu;Dong Li;Hou-cheng Zhang;P. Wang;
中科院分区：
文献类型：
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作者：
Huajie Zhang;Bin Wang;Zhongrui Ma;Mohui Wei;Jun O. Liu;Dong Li;Hou-cheng Zhang;P. Wang;
基于黑色素瘤相关抗原（MAGE）的疫苗为肿瘤免疫治疗提供了一种有前途的策略，尽管免疫原性较弱。在该研究中，异种抗原L-鼠李糖（Rha）与截短的MAGE-A3（tMAGE-A3）化学缀合以产生Rha-tMAGE-A3。该产品与人血清中纯化的抗Rha抗体具有良好的抗原性。FITC标记的Rha-tMAGE-A3在THP-1人巨噬细胞中通过抗Rha抗体依赖性抗原摄取过程检测到。此外，与用tMAGE-A3刺激的PBMC相比，在存在抗Rha抗体的情况下用Rha-tMAGE-A3刺激的外周血单核细胞（PBMC）对由MAGE-A3抗原表面化的A375人黑素瘤细胞显示出更好的细胞毒性。所有数据表明，Rha表位与法师的连接通过利用人天然存在的抗Rha抗体的免疫效应子功能增强了法师的免疫原性。Rha表位可作为肿瘤相关抗原的免疫增强剂，用于肿瘤免疫治疗的研究。
Vaccines based on melanoma-associated antigens (MAGEs) present a promising strategy for tumor immunotherapy, albeit with weak immunogenicity. In this study, the xenoantigen L-rhamnose (Rha) was chemically conjugated with truncated MAGE-A3 (tMAGE-A3) to generate Rha-tMAGE-A3. The product showed good antigenicity with anti-Rha antibodies purified from human serum. FITC-labeled Rha-tMAGE-A3 was detected in THP-1 human macrophage cells via the anti-Rha antibody-dependent antigen uptake process. Furthermore, peripheral blood mononuclear cells (PBMCs) stimulated with Rha-tMAGE-A3 in the presence of anti-Rha antibodies showed better cytotoxicity toward A375 human melanoma cells surfaced by MAGE-A3 antigen compared to PBMCs stimulated with tMAGE-A3. All data reveal that linking of Rha epitopes to MAGE enhances the immunogenicity of MAGE by harnessing the immune effector functions of human naturally existing anti-Rha antibodies. Rha epitopes could become immunogenicity enhancers of tumor associated antigens in the development of tumor immunotherapies.