Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Islamic Republic of Iran.
Monoclon Antib Immunodiagn Immunother. 2021 Jun;40(3):113-117. doi: 10.1089/mab.2020.0043. Epub 2021 Jun 1.
Immunotoxins, as a class of antitumor agents, consist of tumor-selective ligands linked to highly toxic protein molecules. This type of modified antibody has been designed for the therapy of cancers and a few viral infections. In this study, we designed immunotoxin consisting of mouse programmed cell death protein-1 (PD1), which genetically fused to diphtheria toxin (DT) subunit A (DT386). DNA construct was cloned, expressed in a bacterial system, purified, and confirmed by western blotting. The immunotoxin potency in the treatment of tumorous C57BL/6 mice was evaluated. Immunotoxin was injected intratumoral to mice, and through eight injections, 67% of the tumor volume of the test group started shrinking dramatically. On the contrary, the tumor size of the control group, treated with phosphate-buffered saline, continued its growth. The successful targeting of solid tumor cells by PD1-DT immunotoxin demonstrates the potential therapeutic utility of these conjugates.
免疫毒素是一类抗肿瘤药物，由与高毒性蛋白分子连接的肿瘤选择性配体组成。这种经过修饰的抗体被设计用于治疗癌症和一些病毒感染。在这项研究中，我们设计了一种由小鼠程序性细胞死亡蛋白 1（PD1）组成的免疫毒素，该蛋白与白喉毒素（DT）亚单位 A（DT386）基因融合。DNA 构建体被克隆、在细菌系统中表达、纯化，并通过 Western blot 进行确认。评估了免疫毒素在治疗 C57BL/6 荷瘤小鼠中的功效。免疫毒素被注射到肿瘤内，经过 8 次注射，实验组 67%的肿瘤体积开始显著缩小。相比之下，用磷酸盐缓冲盐水治疗的对照组的肿瘤大小继续增长。PD1-DT 免疫毒素对实体肿瘤细胞的成功靶向表明了这些缀合物的潜在治疗用途。
