抗体-鼠李糖复合物的超分子组装增强补体依赖性细胞毒性用于癌症免疫治疗

IF 1.2 4区化学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Carbohydrate Chemistry Pub Date : 2025-03-24 DOI:10.1080/07328303.2024.2418526

Haofei Hong , Kun Zhou , Han Lin , Zhimeng Wu

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引用次数: 0

摘要

增强单克隆抗体（mab）的补体依赖性细胞毒性（CDC）有可能改善其临床性能。在这项研究中，我们描述了一种创新的抗体-半抗原超分子复合物策略来增强CDC活性。我们选择了一种被批准的抗cd20单抗Rituximab (RTX)，并将其与adamantane （Ada）偶联生成RTX-Ada。在靶向cd20阳性细胞后，该缀合物可以通过主客体相互作用与鼠李糖修饰的β-环糊精相互作用，在原位形成一个超分子复合物，可以将抗Rha抗体募集到cd20阳性癌细胞上。该复合物为补体系统激活提供了大量的Fc结构域，从而增强了CDC。我们的研究证明了基于抗体的超分子复合物在癌症免疫治疗中的潜力，为提高基于单克隆抗体的癌症治疗的疗效提供了一种有希望的方法。

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Supramolecular assembly of antibody-rhamnose complex to enhance the complement-dependent cytotoxicity for cancer immunotherapy

Enhancing the complement-dependent cytotoxicity (CDC) of monoclonal antibodies (mAbs) has the potential to improve their clinical performance. In this study, we describe an innovative antibody-hapten supramolecular complex strategy to amplify CDC activity. We selected Rituximab (RTX), an approved anti-CD20 mAb, and conjugated it with adamantane (Ada) to generate RTX-Ada. After targeting CD20-positive cells, this conjugate can interact with rhamnose (Rha)-modified β-cyclodextrin via host-guest interaction, in situ forming a supramolecular complex that can recruit anti-Rha antibodies onto CD20-positive cancer cells. This complex provides a larger number of Fc domains for complement system activation, leading to enhanced CDC. Our study demonstrates the potential of antibody-based supramolecular complexes for cancer immunotherapy, offering a promising approach to improve the efficacy of mAb-based cancer treatments.

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来源期刊

Journal of Carbohydrate Chemistry 化学-生化与分子生物学

CiteScore

2.10

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Carbohydrate Chemistry serves as an international forum for research advances involving the chemistry and biology of carbohydrates. The following aspects are considered to fall within the scope of this journal: -novel synthetic methods involving carbohydrates, oligosaccharides, and glycoconjugates- the use of chemical methods to address aspects of glycobiology- spectroscopic and crystallographic structure studies of carbohydrates- computational and molecular modeling studies- physicochemical studies involving carbohydrates and the chemistry and biochemistry of carbohydrate polymers.