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用于癌症免疫治疗的工程化多特异性纳米抗体

Engineering multi-specific nano-antibodies for cancer immunotherapy.

作者信息

Fan Ya-Nan, Zhu Long, Qing Yu-Xin, Ye Si-Yi, Ye Qian-Ni, Huang Xiao-Yi, Zhao Dong-Kun, Tian Tai-Yu, Li Fang-Chao, Yan Guan-Rong, Yang Xian-Zhu, Shen Song, Wang Jun

机构信息

School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, P. R. China.

National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, P. R. China.

出版信息

Nat Biomed Eng. 2025 Jun 26. doi: 10.1038/s41551-025-01425-5.

Abstract

Immobilizing multiple types of monoclonal antibody (mAb) on nanoparticle surfaces is a promising approach for creating nanomedicines that emulate the functionality of multi-specific antibodies. However, the clinical translation of these multi-specific nano-antibodies (multi-NanoAbs) has been hindered by intricate fabrication procedures, inevitable attenuation in mAb affinity and insufficient carrier biosecurity. Here we develop a versatile nano-adaptor for immobilizing mAbs and construct multi-NanoAbs using a recombinant fusion protein that consists of Fc gamma receptor 1 and serum albumin, along with the biomedical polymer poly(L-lactide). Our findings demonstrate that fusion protein/polymer-based nano-adaptor is facilitated by FcγR1 on its surface to bind mAbs through receptor-ligand interactions rather than complex chemical conjugation and enables convenient and controlled construction of diverse multi-NanoAbs with efficacious therapeutic effects. We achieved large-scale production of humanized fusion protein/polymer-based nano-adaptor and confirmed the antitumour effectiveness of multi-NanoAb in humanized immune system mouse models, highlighting their prospects for clinical translation.

摘要

将多种类型的单克隆抗体(mAb)固定在纳米颗粒表面是一种很有前景的方法,可用于制造模拟多特异性抗体功能的纳米药物。然而,这些多特异性纳米抗体(multi-NanoAbs)的临床转化受到复杂制造程序、mAb亲和力不可避免的衰减以及载体生物安全性不足的阻碍。在此,我们开发了一种用于固定mAb的通用纳米适配器,并使用由Fcγ受体1和血清白蛋白以及生物医学聚合物聚(L-丙交酯)组成的重组融合蛋白构建multi-NanoAbs。我们的研究结果表明,基于融合蛋白/聚合物的纳米适配器在其表面被FcγR1促进,通过受体-配体相互作用而非复杂的化学偶联来结合mAb,并能够方便且可控地构建具有有效治疗效果的多种multi-NanoAbs。我们实现了基于人源化融合蛋白/聚合物的纳米适配器的大规模生产,并在人源化免疫系统小鼠模型中证实了multi-NanoAb的抗肿瘤有效性,突出了它们的临床转化前景。

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