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双功能螯合剂与单抗的连接数量是否会影响其放射性标记物的生物学活性?以 CD-20 单抗为例用 Y 或 Lu 标记进行讨论。

Does the Number of Bifunctional Chelators Conjugated to a mAb Affect the Biological Activity of Its Radio-Labeled Counterpart? Discussion Using the Example of mAb against CD-20 Labeled with Y or Lu.

机构信息

National Centre for Nuclear Research, Radioisotope Centre POLATOM, Otwock 05-400, Poland.

出版信息

J Med Chem. 2022 May 12;65(9):6419-6430. doi: 10.1021/acs.jmedchem.1c02044. Epub 2022 Apr 20.

Abstract

There has been considerable interest in developing a monoclonal antibody (mAb) against-CD-20 (for example, Rituximab) modified by bifunctional chelating agents (BCA) for non-Hodgkin's lymphoma radioimmunotherapy. Therefore, many researchers have modified this monoclonal antibody by attaching different BCA moieties and evaluated their biological activities in terms of in vitro study and in vivo study in healthy and tumor xenografted rodents. This mini-perspective reviews the in vitro studies, the immunoreactivity and physiological distribution studies: organ-to-blood and the tumor-to-organ ratio of conjugates with different numbers of chelators per mAb. We set up a null hypothesis that states there is no statistical significance between the biological activity of monoclonal antibody (Rituximab) and the number of conjugated bifunctional chelators. Overall, we have concluded that there is no strong evidence for this hypothesis. However, the literature data should be questioned due to the potential lack of uniform study methodology.

摘要

人们对开发针对-CD-20(例如,利妥昔单抗)的单克隆抗体(mAb)产生了浓厚的兴趣,这些 mAb 经过双功能螯合剂(BCA)修饰可用于非霍奇金淋巴瘤的放射免疫治疗。因此,许多研究人员通过连接不同的 BCA 部分来修饰这种单克隆抗体,并根据体外研究和健康及肿瘤异种移植啮齿动物的体内研究来评估它们的生物学活性。这篇观点综述回顾了不同 BCA 修饰数量的 mAb 的体外研究、免疫反应性和生理分布研究:器官-血液比和肿瘤-器官比。我们提出了一个零假设,即单克隆抗体(利妥昔单抗)的生物学活性与连接的双功能螯合剂数量之间没有统计学意义。总的来说,我们得出的结论是,没有强有力的证据支持这一假设。然而,由于潜在的缺乏统一的研究方法,文献数据应该受到质疑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69d6/9109692/cc92863a06a0/jm1c02044_0001.jpg

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