Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities
文献类型：期刊论文
| 作者 | Li, Hua-ying2,3,4; Chen, Yi-li3; Deng, Xiang-nan5; Li, Huan-huan3; Tan, Jie3; Liu, Guo-jian6; Zheng, Yu-juan1,2; Pei, Min3,7; Peng, Kai-ting1,2; Yue, Li-li2,8 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2023-06-16 |
| 页码 | 9 |
| 关键词 | cancer immunotherapy B7-H3 PD-L1 bispecific antibodies VHH antibody-dependent cell-mediated cytotoxicity (ADCC) |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-023-01118-2 |
| 通讯作者 | Chen, Yi-li(cheny@dartsbio.com) ; Wang, Chun-he(wangc@simm.ac.cn) |
| 英文摘要 | Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3xPD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-& gamma; production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3xPD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors. |
| WOS关键词 | IFN-GAMMA ; B7 FAMILY ; EXPRESSION ; CANCER ; CARCINOMA ; CELLS ; DIFFERENTIATION ; INHIBITION ; BLOCKADE ; MOLECULE |
| 资助项目 | National Natural Science Foundation of China[81872785] ; Shanghai Municipal Commission of Science and Technology of China[21S11904500] ; Major Scientific and Technological Special Project of Zhongshan City[191022172638719] ; Major Scientific and Technological Special Project of Zhongshan City[210205143867019] ; CAS Bohai Rim Advanced Research Institute for Drug Discovery Project[LX211005] ; Research amp; Development Plan in Key Areas of Guangdong Province[2022B1111070007] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001012289900001 |
| 出版者 | NATURE PUBL GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306328]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Yi-li; Wang, Chun-he |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Biotherapeut Discovery Res Ctr, Shanghai 201203, Peoples R China 3.Shanghai Mabstone Biotechnol Ltd, Shanghai 201203, Peoples R China 4.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Dartsbio Pharmaceut Ltd, Zhongshan 528400, Peoples R China 7.Jinan Univ, Inst Biomed & Dept Cell Biol, Natl Engn Res Ctr Genet Med, Guangzhou 510632, Peoples R China 8.China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 211198, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Hua-ying,Chen, Yi-li,Deng, Xiang-nan,et al. Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities[J]. ACTA PHARMACOLOGICA SINICA,2023:9. |
| APA | Li, Hua-ying.,Chen, Yi-li.,Deng, Xiang-nan.,Li, Huan-huan.,Tan, Jie.,...&Wang, Chun-he.(2023).Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities.ACTA PHARMACOLOGICA SINICA,9. |
| MLA | Li, Hua-ying,et al."Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities".ACTA PHARMACOLOGICA SINICA (2023):9. |
入库方式： OAI收割
来源：上海药物研究所
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