School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; Department of Zoology, Lahore College for Women University, Pakistan.
Int Immunopharmacol. 2021 Jan;90:107155. doi: 10.1016/j.intimp.2020.107155. Epub 2020 Nov 23.
IL13Rα2 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-2monoclonal antibody mAb15D8 on lung cancer cells in vitro and in vivo by blocking its specific epitope in IL13Rα2 antigen. The mAb15D8 blocking epitope was analyzed through the mutagenesis of IL13Rα2 and confirmed with western blot. We found that the IL13Rα2 epitope recognized by mAb15D8 antibody is a new binding site localized in the fibronectin-III domain-1 of IL13Rα2 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 IL13Rα2 which binds to specific epitope on IL13Rα2 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.
白细胞介素 13 受体α2 （IL13Rα2）在多种类型的肿瘤中高表达，由于其预后不良，可成为人类癌症治疗的靶点。本研究旨在通过阻断 IL13Rα2 抗原的特异性表位，来鉴定和研究白细胞介素 13 受体亚单位α-2 单克隆抗体 mAb15D8 对肺癌细胞的体外和体内作用。通过对 IL13Rα2 的突变分析了 mAb15D8 的阻断表位，并通过 Western blot 进行了验证。我们发现 mAb15D8 抗体识别的 IL13Rα2 表位是一个位于 IL13Rα2 抗原的纤维连接蛋白-III 结构域 1 中的新结合位点。此外，mAb15D8 明显降低了 H460、A549、SKOV3 和 B16F10 细胞的增殖和迁移。mAb15D8 治疗显著降低了裸鼠 H460 异种移植瘤的形成和生长，并抑制了 B16F10 肿瘤转移，提高了 C57BL/6 小鼠的存活率。药代动力学和毒理学分析表明 mAb15D8 作为一种潜在的治疗剂是安全的。我们开发了一种针对 IL13Rα2 的新型鼠单克隆抗体，该抗体与 IL13Rα2 抗原上的特定表位结合。体内治疗用抗体显著降低了肿瘤生长和肺转移，并延长了存活时间。这些结果表明 mAb15D8 抗体作为一种潜在的癌症治疗剂具有治疗潜力。
