Ofatumumab and Granzyme B as immunotoxin against CD20 antigen.

Fateme Sefid, Armina Alagheband Bahrami, Zahra Payandeh, Saeed Khalili, Ghasem Azamirad, Seyed Mehdy Kalantar, Maryam Touhidinia
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引用次数: 1

Abstract

Anti-CD20 antibodies such as ofatumumab has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. In this study, we have designed an immunotoxin composed of Granzyme B and the high affinity variant of Ofatumumab. Different simulation software applied to explore the structure of Granzyme B, a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator was attached to its specific antibody structure (Ofatumumab) via an adaptor sequence. The accuracy, energy minimization and characterization of biological properties of the final structure were evaluated. Our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. The precise and accurate design of the immune-therapeutic agents against cancer cells can be confirmed by employment of in-silico approaches. Consequently, based on this approach we could introduce a capable immunotoxin which specifically targeting CD20 in an accurate orientation and initiates cancer cell destruction by its toxin domain.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-022-00120-6.

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Ofatumumab和颗粒酶B作为CD20抗原的免疫毒素。
抗cd20抗体如ofatumumab已被证明对复发/难治性慢性淋巴细胞白血病有效,是迄今为止最成功的治疗方法之一。在这项研究中,我们设计了一种由颗粒酶B和Ofatumumab的高亲和力变体组成的免疫毒素。应用不同的模拟软件来探索颗粒酶B的结构,颗粒酶B是细胞毒性淋巴细胞颗粒中的丝氨酸蛋白酶,作为一种凋亡介质,通过适配器序列连接到其特异性抗体结构(Ofatumumab)上。评估了最终结构的准确性、能量最小化和生物特性表征。我们的计算结果表明,所采用的结构预测方法已经成功地设计了免疫毒素的结构。针对癌细胞的免疫治疗剂的精确和准确的设计可以通过采用计算机方法来证实。因此,基于这种方法,我们可以引入一种能够精确定向特异性靶向CD20的免疫毒素,并通过其毒素域启动癌细胞破坏。补充信息:在线版本包含补充资料,提供地址为10.1007/s40203-022-00120-6。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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