双特异性抗体及纳米技术在肿瘤免疫治疗中的应用进展

许仕琳; 许海燕

doi:10.12211/2096-8280.2021-045

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双特异性抗体及纳米技术在肿瘤免疫治疗中的应用进展

特约评述 | 更新时间：2025-03-20

- 双特异性抗体及纳米技术在肿瘤免疫治疗中的应用进展
- Progress of bispecific antibodies and nanotechnology in tumor immunotherapies
- 合成生物学 2022年3卷第2期页码：352-368
- 作者机构：
  
  中国医学科学院基础医学研究所，北京协和医学院基础学院，北京 100005
- 作者简介：
  
  [ "许仕琳（1993—），女，博士研究生。研究方向为化学合成拮抗多肽和纳米药物递送系统在急性髓系白血病中的应用。 E-mail：1316870420@qq.com" ]
  [ "许海燕（1962—），女，研究员，博士生导师。研究方向为应用纳米技术发展抗肿瘤治疗药物和多药共递送系统、纳米结构生物材料调控细胞行为和引导组织再生与修复和纳米毒理学和纳米材料安全应用评价方法等。 E-mail：xuhy@pumc.edu.cn" ]
- 基金信息：
  
  国家自然科学基金(NSFC81870133);中国医学科学院医学与健康科技创新工程(2016-I2M-3-004)
- DOI：10.12211/2096-8280.2021-045
  中图分类号： R 318
- 收稿：2021-04-13，
  
  修回：2021-07-29，
  
  纸质出版：2022-04-30
- 稿件说明：
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许仕琳，许海燕. 双特异性抗体及纳米技术在肿瘤免疫治疗中的应用进展［J］. 合成生物学， 2022， 3（2）： 352-368

XU Shilin， XU Haiyan. Progress of bispecific antibodies and nanotechnology in tumor immunotherapies［J］. Synthetic Biology Journal， 2022， 3（2）： 352-368
许仕琳，许海燕. 双特异性抗体及纳米技术在肿瘤免疫治疗中的应用进展［J］. 合成生物学， 2022， 3（2）： 352-368 DOI： 10.12211/2096-8280.2021-045.

XU Shilin， XU Haiyan. Progress of bispecific antibodies and nanotechnology in tumor immunotherapies［J］. Synthetic Biology Journal， 2022， 3（2）： 352-368 DOI： 10.12211/2096-8280.2021-045.

摘要

单克隆抗体已经广泛用于肿瘤的靶向治疗，但由于肿瘤属于异质性疾病，涉及介导疾病进展的多种配受体信号变化以及信号级联通路之间的交互作用。因此，针对单一抗原的治疗难以有效抑制疾病的进程，而阻断多种不同的病理因素和途径是有望提高治疗效果的重要途径。近年来，合成生物学、生物工程和纳米技术等在不断发展，利用这些技术来设计工程化的治疗性抗体或可为肿瘤靶向免疫治疗带来新的思路。双特异性抗体是一种具有两种抗体特异性的人工抗体，可以同时识别不同的抗原或表位，由此实现多种功能，例如可以将T细胞重定向至肿瘤细胞并同时阻断两条不同的或相互串扰的细胞信号传导通路；与此同时，备受关注的纳米载体技术则为双抗体药物的研发与应用提供了有利的新工具。本文首先对双特异性抗体的生产和制备做简要介绍，然后对双特异性抗体在恶性血液肿瘤（急性髓细胞白血病和B细胞恶性血液肿瘤）和实体瘤（乳腺癌、卵巢癌、肺癌和头颈癌等）免疫治疗中的应用进展做分类介绍，并进一步介绍了双特异性抗体与纳米技术相结合形成的递送系统在肿瘤免疫治疗中的研究进展；最后讨论了双特异性抗体在设计和医学应用中面临的问题，并展望了纳米技术介导的靶向治疗策略在肿瘤治疗中的应用前景，以及双特异性抗体与免疫检查点抑制剂或疫苗等其他疗法联合应用的可能。

Abstract

Monoclonal antibodies have been widely used in tumor therapy. However

the effects of monoclonal anti-tumor antibodies for treating tumor are still limited as tumor is a heterogeneous disease involving a variety of disease-mediated alterations in ligands and receptors as well as signaling cascades crosstalk. Therefore

it is difficult to suppress tumor progression by targeting single antigen or epitope. Blocking different pathological factors/pathways at the same time is thus becoming a promising strategy for tumor treatment to improve therapeutic efficacy. In recent years

bispecific antibody-based drugs have attracted increasing research attention as novel therapeutic strategies in liquid and solid tumors

thanks to the remarkable progress made in the synthetic biology

bioengineering and nanotechnology. Bispecific antibody is an artificially engineering-modified antibody capable of binding two distinct antigens/epitopes simultaneously to increase selectivity to tumors

and consequently induce a powerful anti-tumor immune response. Due to their low immunogenicity

good stability and easy preparation

a variety of bispecific antibody formats have been developed

mainly including full-length bispecific antibodies and derivatives that lack Ig domains

trifunctional bispecific antibodies

bispecific T cell engagers (BiTEs)

dual affinity retargeting (DART) antibodies and bispecific nanoplatforms/nanobodies. Bispecific antibody-based drugs are of great significance to tumor immunotherapy in following aspects: 1) obtains stronger specific capacity of capturing tumor cells to reduce antigen-loss escape

2) activate and recruit immune effector cells such as T lymphocytes and natural killer cells to enhance tumor cells killing

and 3) influence two different receptors or signaling pathways concurrently that display unique or overlapping functions in the pathogenetic process. At the same time

nanotechnologies are being largely involved into the development of multiple bispecific antibodies. This article briefly comments on the production of bispecific antibodies

and also highlights the progress of bispecific antibodies and their combination with nanotechnology-based delivery systems in the application of immunotherapy for hematological malignancies and solid tumors.

关键词

Keywords

references

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