奥法木单抗和颗粒酶B作为针对CD20抗原的免疫毒素
Ofatumumab and Granzyme B as immunotoxin against CD20 antigen.
作者信息
Sefid Fateme, Alagheband Bahrami Armina, Payandeh Zahra, Khalili Saeed, Azamirad Ghasem, Kalantar Seyed Mehdy, Touhidinia Maryam
机构信息
Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran.
Department of Biology, Science and Art University, Yazd, Iran.
出版信息
In Silico Pharmacol. 2022 Mar 18;10(1):6. doi: 10.1007/s40203-022-00120-6. eCollection 2022.
UNLABELLED
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.
未标注
抗CD20抗体，如奥法木单抗，已在复发/难治性慢性淋巴细胞白血病中显示出疗效，是迄今为止最成功的治疗方法之一。在本研究中，我们设计了一种由颗粒酶B和奥法木单抗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一种丝氨酸蛋白酶，作为凋亡介质，通过接头序列连接到其特异性抗体结构（奥法木单抗）上。评估了最终结构的准确性、能量最小化和生物学特性表征。我们的计算结果表明，所采用的结构预测方法已成功设计出免疫毒素结构。通过使用计算机模拟方法可以证实针对癌细胞的免疫治疗剂的精确设计。因此，基于这种方法，我们可以引入一种有能力的免疫毒素，它以精确的方向特异性靶向CD20，并通过其毒素结构域引发癌细胞破坏。
补充信息
在线版本包含可在10.1007/s40203-022-00120-6获取的补充材料。
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