A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer
A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer
复制标题
新型靶向抗白细胞介素13受体亚基α2单克隆抗体抑制肺癌肿瘤生长和转移
DOI：
10.1016/j.intimp.2020.107155
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发表时间：
2021-01-12
影响因子：
5.6
通讯作者：
Li, Dawei
中科院分区：
文献类型：
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作者：
Raza, Ghulam;Yunus, Fakhar-un-Nisa;Li, Dawei
IL 13 R α 2在不同类型的肿瘤中显示出高表达，并且由于其预后不良而可以成为人类癌症治疗的靶点。本研究的目的是研究白细胞介素13受体α 2亚单位单克隆抗体mAb 15 D8通过阻断其在白细胞介素13受体α 2抗原上的特异性表位对肺癌细胞的作用。通过IL 13 R α 2的诱变分析mAb 15 D8封闭表位，并用蛋白质印迹法证实。我们发现由mAb 15 D8抗体识别的IL 13 R α 2表位是位于IL 13 R α 2抗原的纤连蛋白-III结构域-1的新结合位点。此外，mAb 15 D8明显抑制H460、A549、SKOV 3和B16 F10细胞的增殖和迁移。用mAb 15 D8处理显著降低了裸鼠中H460异种移植肿瘤的形成和生长，并抑制了C57 BL/6小鼠中B16 F10肿瘤转移和增加了存活。药代动力学和毒理学分析证明了mAb 15 D8作为潜在治疗剂的安全性。我们开发了一种新的抗IL 13 R α 2的小鼠单克隆抗体，其结合IL 13 R α 2抗原上的特异性表位。用抗体进行体内治疗显著降低了肿瘤生长和肺转移，延长了存活期。这些结果提示mAb 15 D8抗体作为用于癌症治疗的潜在治疗剂。
IL13R alpha 2 shows high expression in different types of tumors and can be a target for cancer therapy in humans due to its poor prognosis. The aim of our study is to characterize and investigate the effect of interleukin-13 receptor subunit alpha-2 monoclonal antibody mAb15D8 on lung cancer cells in vitro and in vivo by blocking its specific epitope in IL13R alpha 2 antigen. The mAb15D8 blocking epitope was analyzed through the mutagenesis of IL13R alpha 2 and confirmed with western blot. We found that the IL13R alpha 2 epitope recognized by mAb15D8 antibody is a new binding site localized in the fibronectin-III domain-1 of IL13R alpha 2 antigen. Moreover, the mAb15D8 obviously reduced cell proliferation, migration of H460, A549, SKOV3, and B16F10 cells. Treatment with mAb15D8 significantly reduced the H460 xenograft tumor formation and growth in nude mice and inhibited B16F10 tumor metastasis and increased survival in C57BL/6 mice. Pharmacokinetic and toxicological analysis demonstrated the safety of mAb15D8 as a potential therapeutic agent. We developed a novel mouse monoclonal antibody against IL13R alpha 2 which binds to specific epitope on IL13R alpha 2 antigen. In vivo treatment with the antibody significantly reduced tumor growth and lung metastasis and prolonged survival. These results suggest mAb15D8 antibody as a potential therapeutic agent for cancer therapy.