小柯机器人

A Chimeric Conjugate of Antibody and Programmable DNA Nanoassembly Smartly Activates T cell for Precise Cancer Cell Targeting
2022-06-29 16:36

湖南大学聂舟团队开发出一种抗体和可编程DNA纳米组装的嵌合物,巧妙地激活T细胞以精确靶向癌细胞。相关研究成果于2022年6月24日发表在国际顶尖学术期刊《德国应用化学》。

综合引导T细胞对抗肿瘤是免疫治疗中一种很有前景的策略,而巧妙地使T细胞产生可调节的免疫反应仍然是一个挑战。

该文中,研究人员报告了一个智能分子平台,用于设计T细胞识别,以选择性激活,从而潜在地杀死癌细胞。为此,研究人员制造了一种杂交结合物,该结合物使用点击型DNA-蛋白质结合物为T细胞结合抗体配备两个不同的可编程DNA纳米组装体。通过在动态DNA电路中集成多个适体抗原识别,在高阶逻辑运算后实现了对癌细胞上三重抗原的组合识别,以选择性激活T细胞。

此外,通过耦合DNA纳米结构,研究人员精确地定义了抗原结合适体的价态,以调节亲和力,在体外和体内实现有效的肿瘤消除。综上所述,研究人员提出了一种多功能和可编程的综合免疫治疗策略。

附:英文原文

Title: A Chimeric Conjugate of Antibody and Programmable DNA Nanoassembly Smartly Activates T cell for Precise Cancer Cell Targeting

Author: Rui Tang, Yu-Hao Fu, Bo Gong, Ying-Ying Fan, Hong-Hui Wang, Yan Huang, Zhou Nie, Ping Wei

Issue&Volume: 2022-06-24

Abstract: Synthetically directing T-cell against tumor emerges as a promising strategy in immunotherapy, while it remains challenging to smartly engage T cells with tunable immune response. Herein, we report an intelligent molecular platform to engineer T-cell recognition for selective activation to potently kill cancer cells. To this end, we fabricated a hybrid conjugate that uses a click-type DNA-protein conjugation to equip the T cell-engaging antibody with two distinct programmable DNA nanoassemblies.  By integrating multiple aptameric antigen-recognitions within a dynamic DNA circuit, we achieved combinatorial recognition of triple-antigens on cancer cells for selective T-cell activation after high-order logic operation. Moreover, by coupling a DNA nanostructure, we precisely defined the valence of the antigen-binding aptamers to tune avidity, realizing effective tumor elimination  in vitro  and  in vivo. Together, we present a versatile and programmable strategy for synthetic immunotherapy.

DOI: 10.1002/anie.202205902

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202205902

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