A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer

被引：6

作者：

Raza, Ghulam ^{[1
]}

Yunus, Fakhar-un-Nisa ^{[1
,2
]}

Mangukiya, Hitesh Bhagavanbhai ^{[1
]}

Merugu, Siva Bharath ^{[1
]}

Mashausi, Dhahiri Saidi ^{[1
]}

Wang Zeling ^{[1
]}

Negi, Hema ^{[1
]}

Zhou, Bingjie ^{[1
]}

Roy, Debmalya ^{[1
]}

Wu, Zhenghua ^{[3
]}

Li, Dawei ^{[1
,4
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Pharm, 800 Dongchuan Rd,Minhang Campus, Shanghai 200240, Peoples R China

[2] Lahore Coll Women Univ, Dept Zool, Lahore, Pakistan

[3] Shanghai Jiao Tong Univ, Peoples Hosp, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Minist Educ, Engn Res Ctr Cell & Therapeut Antibody, Shanghai, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2021年 / 90卷

基金：

中国国家自然科学基金;

关键词：

mAb15D8; Anti-IL13R alpha 2 monoclonal antibody; Epitope; Lung metastasis; Pharmacokinetics; Toxicology; HERCEPTIN; EXPRESSION; THERAPY; PROTEIN; CELLS; IL-4;

D O I：

10.1016/j.intimp.2020.107155

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：8

共 39 条

[1] Functional definition of relevant epitopes on the tumor suppressor PTEN protein [J].