Novel IL13RA2-targeted immunocytokines exhibit superior antitumor activities
文献类型：期刊论文
| 作者 | Jing, Qing-qing3; Wen, Jing2; Ou, Jian-xia3; He, Yan-ting2; Zhang, Yu-ting3; Rana, Gul E.3; Wang, Qi3; Wang, Gui-feng1,2,3; Wang, Chun-he1,2,3 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2025-08-12 |
| 页码 | 13 |
| 关键词 | IL13RA2-positive tumors immunocytokines interleukin-2 interleukin-12 |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-025-01611-w |
| 通讯作者 | Wang, Gui-feng(gfwang@simm.ac.cn) ; Wang, Chun-he(wangc@simm.ac.cn) |
| 英文摘要 | Th1-type cytokines such as interleukin-2 (IL-2) and interleukin-12 (IL-12) are known for their potent antitumor activities, but their clinical application has been hindered by significant side effects. Immunocytokines (ICs) that combine cytokines with antibodies have shown favorable therapeutic and safety outcomes in clinical trials. In this study we first investigated the expression patterns and prognostic significance of IL13RA2 across various cancer types through a comprehensive analysis of the TIMER2 and TCGA datasets. Subsequently, we generated 52B8, a neutralizing antibody against interleukin-13 receptor alpha 2 (IL13RA2) as well as three ICs incorporating interleukin-2 (IL-2), interleukin-12 (IL-12), or both, designed as 52B8-IL2, 52B8-IL12 and 52B8-IL2/12, respectively. The ICs exhibited potent and dose-dependent anticancer activity both in vitro and in MC38-hIL13RA2-GFP and A375 tumor xenograft models in vivo. In addition, they exhibited significantly reduced side effects through targeted cytokine delivery as well as enhanced immune cell infiltration into tumors. Collectively, our results suggest that IL13RA2-targeting ICs represent a promising therapeutic strategy for the treatment of IL13RA2-positive tumors. |
| WOS关键词 | MALIGNANT GLIOMAS ; FUSION PROTEIN ; T-CELLS ; IL-12 ; ANTIBODY ; INTERLEUKIN-12 ; CYTOKINES ; EXPRESSION ; FAMILY ; CANCER |
| 资助项目 | Key-Area Research and Development Program of Guangdong Province[2022B1111070007] ; National Natural Science Foundation of China[81872785] ; National Natural Science Foundation of China[32370958] ; Shanghai Municipal Commission of Science and Technology of China[21S11904500] ; Major Scientific and Technological Special Project of Zhongshan City[210205143867019] ; CAS Bohai Rim Advanced Research Institute for Drug Discovery Project[LX211005] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001547876300001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321207]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Gui-feng; Wang, Chun-he |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Biotherapeut Discovery Res Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jing, Qing-qing,Wen, Jing,Ou, Jian-xia,et al. Novel IL13RA2-targeted immunocytokines exhibit superior antitumor activities[J]. ACTA PHARMACOLOGICA SINICA,2025:13. |
| APA | Jing, Qing-qing.,Wen, Jing.,Ou, Jian-xia.,He, Yan-ting.,Zhang, Yu-ting.,...&Wang, Chun-he.(2025).Novel IL13RA2-targeted immunocytokines exhibit superior antitumor activities.ACTA PHARMACOLOGICA SINICA,13. |
| MLA | Jing, Qing-qing,et al."Novel IL13RA2-targeted immunocytokines exhibit superior antitumor activities".ACTA PHARMACOLOGICA SINICA (2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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