A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer
•We generated a novel target anti-IL13Rα2 monoclonal antibody 15D8 through hybridoma technique.•mAb15D8 binds to a specific epitope of IL13Rα2 antigen from 57 to 71 amino acids.•mAb15D8 inhibited tumor growth and metastasis in lung cancer.•It exerts no toxic effects on major organs of mice.•This ant...
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Veröffentlicht in: | International immunopharmacology 2021-01, Vol.90, p.107155, Article 107155 |
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Sprache: | eng |
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Zusammenfassung: | •We generated a novel target anti-IL13Rα2 monoclonal antibody 15D8 through hybridoma technique.•mAb15D8 binds to a specific epitope of IL13Rα2 antigen from 57 to 71 amino acids.•mAb15D8 inhibited tumor growth and metastasis in lung cancer.•It exerts no toxic effects on major organs of mice.•This antibody opens up a unique opportunity to study its therapeutic potential.
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. |
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ISSN: | 1567-5769 1878-1705 |
DOI: | 10.1016/j.intimp.2020.107155 |