The Application of Nanobody in CAR-T Therapy.

文献信息

DOI	10.3390/biom11020238
PMID	33567640
期刊	Biomolecules
影响因子	4.8
JCR 分区	Q1
发表年份	2021
被引次数	56
关键词	BCMA, CAR-T, VHH, 纳米抗体
文献类型	Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN	2218-273X
期号	11(2)
作者	Chaolemeng Bao, Quanli Gao, Lin-Lin Li, Lu Han, Bingxiang Zhang, Yijin Ding, Zongpei Song, Ruining Zhang, Jishuai Zhang, Xian-Hui Wu

一句话小结

本研究探讨了纳米抗体在嵌合抗原受体（CAR）T细胞疗法中的应用，发现基于纳米抗体的CAR-T细胞在多种肿瘤靶点上展现出与传统单链可变片段（scFv）相似的抗肿瘤效果。这一发现不仅验证了纳米抗体的临床潜力，也为CAR-T疗法的进一步发展提供了新的思路。

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BCMA · CAR-T · VHH · 纳米抗体

摘要

嵌合抗原受体（CAR）T细胞疗法是一种具有临床疗效和特定靶点的免疫细胞疗法。典型的嵌合抗原受体（CAR）结构由抗原结合域、跨膜域和细胞质域组成。由于其小巧的尺寸、优良的稳定性、高亲和力和制造可行性，纳米抗体已被广泛应用于CAR-T的抗原结合域。基于纳米抗体的CAR结构在十多种不同的肿瘤特异性靶点中已证明其功能。经过转导至Jurkat细胞、自然杀伤细胞或原代T细胞后，所产生的基于纳米抗体的CAR-T或CAR-NK细胞在体外和体内均显示出抗肿瘤效果。有趣的是，由单一纳米抗体或双价纳米抗体调节的抗BCMA CAR-T，其临床效果与单链可变片段（scFv）调节的CAR-T相当。纳米抗体在CAR-T疗法中的应用已从基础研究到临床实践得到充分验证，并在应对更具挑战性的任务时展现出巨大的潜力。

英文摘要

Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The application of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.

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主要研究问题

核心洞察

研究背景和目的

CAR-T细胞疗法是一种有效的免疫细胞疗法，主要用于治疗血液肿瘤。尽管其在某些血液恶性肿瘤中显示出良好的临床效果，但在实体瘤中的应用仍面临挑战。纳米抗体（nanobody）因其小尺寸、高亲和力和稳定性，逐渐成为CAR-T疗法中抗原结合域的理想选择。本研究旨在探讨纳米抗体在CAR-T疗法中的应用及其潜在优势。

主要方法/材料/实验设计

研究通过文献综述和案例分析，系统总结了纳米抗体在CAR-T疗法中的应用。实验设计主要包括以下几个步骤：

文献回顾：分析纳米抗体的结构和功能特点。
纳米抗体特性分析：研究其在CAR-T疗法中的优势，包括稳定性、亲和力和生产可行性。
纳米抗体在CAR-T中的应用：总结已有的纳米抗体CAR-T构建案例。
临床试验数据汇总：对比不同纳米抗体CAR-T的临床效果。
比较不同CAR-T疗法的效果：分析纳米抗体与传统scFv的比较。

关键结果和发现

纳米抗体具有较小的分子量和较高的稳定性，能够有效结合多种肿瘤特异性抗原。
研究表明，纳米抗体在CAR-T细胞中展现出与scFv相似的抗肿瘤效果。
临床数据表明，基于纳米抗体的CAR-T疗法在治疗复发/难治性多发性骨髓瘤（如PRG1801）中表现出良好的疗效。

主要结论/意义/创新性

纳米抗体为CAR-T疗法提供了一种新的抗原结合域选择，具有较低的免疫原性和更好的稳定性。纳米抗体构建的CAR-T细胞在临床上显示出与传统scFv构建的CAR-T细胞相似的疗效，并可能在未来的肿瘤免疫治疗中发挥重要作用。这一研究为CAR-T疗法的优化提供了新的思路和方向。

研究局限性和未来方向

目前关于纳米抗体的临床数据仍较为有限，需要更多的临床试验来验证其长期效果和安全性。
未来研究可集中在优化纳米抗体的选择、改进CAR-T细胞的制造工艺以及探索其在其他类型肿瘤中的应用潜力。

研究方面	结果描述
纳米抗体特性	小尺寸、高亲和力、低免疫原性
CAR-T疗法效果	与scFv构建的CAR-T细胞效果相似
临床试验	PRG1801显示出良好的疗效，适用于复发/难治性多发性骨髓瘤

通过这一研究，纳米抗体在CAR-T细胞治疗中的应用前景得到了进一步的验证，未来有望在更广泛的癌症治疗中发挥重要作用。

参考文献

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Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells. - Hongxia Wang;Liyan Wang;Yanning Li;Guangqi Li;Xiaochun Zhang;Dan Jiang;Yanting Zhang;Liyuan Liu;Yuankui Chu;Guangxian Xu - Cancer cell international (2021)
Transportation of Single-Domain Antibodies through the Blood-Brain Barrier. - Eduardo Ruiz-López;Alberto J Schuhmacher - Biomolecules (2021)
INDI-integrated nanobody database for immunoinformatics. - Piotr Deszyński;Jakub Młokosiewicz;Adam Volanakis;Igor Jaszczyszyn;Natalie Castellana;Stefano Bonissone;Rajkumar Ganesan;Konrad Krawczyk - Nucleic acids research (2022)
A comprehensive comparison between camelid nanobodies and single chain variable fragments. - Yasaman Asaadi;Fatemeh Fazlollahi Jouneghani;Sara Janani;Fatemeh Rahbarizadeh - Biomarker research (2021)
Engineered NK Cells Against Cancer and Their Potential Applications Beyond. - Maria Karvouni;Marcos Vidal-Manrique;Andreas Lundqvist;Evren Alici - Frontiers in immunology (2022)
Development and comparison of three 89Zr-labeled anti-CLDN18.2 antibodies to noninvasively evaluate CLDN18.2 expression in gastric cancer: a preclinical study. - Guilan Hu;Wenjia Zhu;Yu Liu;Yuan Wang;Zheng Zhang;Shikun Zhu;Wenwen Duan;Peipei Zhou;Chao Fu;Fang Li;Li Huo - European journal of nuclear medicine and molecular imaging (2022)
VHH Structural Modelling Approaches: A Critical Review. - Poonam Vishwakarma;Akhila Melarkode Vattekatte;Nicolas Shinada;Julien Diharce;Carla Martins;Frédéric Cadet;Fabrice Gardebien;Catherine Etchebest;Aravindan Arun Nadaradjane;Alexandre G de Brevern - International journal of molecular sciences (2022)
Revolution of CAR Engineering For Next-Generation Immunotherapy In Solid Tumors. - Tao Yu;Shao-Kun Yu;Yan Xiang;Kai-Hua Lu;Ming Sun - Frontiers in immunology (2022)
Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response. - Dong-Rui Wang;Xian-Lin Wu;Ying-Li Sun - Signal transduction and targeted therapy (2022)
CAR-T cell potency: from structural elements to vector backbone components. - Marzieh Mazinani;Fatemeh Rahbarizadeh - Biomarker research (2022)

... (46 更多篇文献)

The Application of Nanobody in CAR-T Therapy. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​