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Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma | |
2023-09-05 | |
发表期刊 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (IF:6.0[JCR-2023],6.1[5-Year]) |
ISSN | 0223-5234 |
EISSN | 1768-3254 |
卷号 | 257 |
发表状态 | 已发表 |
DOI | 10.1016/j.ejmech.2023.115489 |
摘要 | B7-H3 (immunoregulatory protein B7-homologue 3) is overexpressed in many cancer cells with limited expression in normal tissues, considered to be a promising target for tumor therapeutics. Clinical trials of antibody-drug conjugates (ADCs) against different targets for glioblastoma have been investigated and showed potent efficacies. In this study, we developed a homogeneous ADC 401-4 with a drug-to-antibody ratio (DAR) of 4, which was prepared by conjugation of Monomethyl auristatin E (MMAE) to a humanized anti-B7-H3 mAb 401, through a divinylsulfonamide-mediated disulfide re-bridging approach. In vitro studies, 401-4 displayed specific killing against B7-H3-expressing tumors and was more effective in cells with higher levels of B7-H3 for different glioblastoma cells. 401-4 was furthered labeled with Cy5.5 to yield a fluorescent conjugate 401-4-Cy5.5. The vivo imaging studies showed that the conjugate accumulated in tumor regions and exhibited the ability to target-specific delivery. In addition, significant antitumor activities for 401-4 was observed against U87-derived tumor xenografts in a dose dependent manner. |
关键词 | B7-H3 Antibody-drug conjugates Glioblastoma In vivo imaging |
URL | 查看原文 |
收录类别 | SCI |
语种 | 英语 |
资助项目 | Key R & D Program of Jiangsu Province[BE2021644] ; Science and Technology Plan of Suzhou[SKY2022046] ; Key Project of Jiangsu Provincial Health Commission[zd2021050] |
WOS研究方向 | Pharmacology & Pharmacy |
WOS类目 | Chemistry, Medicinal |
WOS记录号 | WOS:001009244400001 |
出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/316419 |
专题 | 免疫化学研究所 生命科学与技术学院 免疫化学研究所_特聘教授组_抗体化学实验室 生命科学与技术学院_硕士生 物质科学与技术学院_硕士生 生命科学与技术学院_博士生 |
共同第一作者 | Wei, Ding; Fu, Fengqing |
通讯作者 | Zhang, Xueguang; Jiang, Biao; Chen, Hongli |
作者单位 | 1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China 4.Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Clin Immunol, 178 Ganjiang Rd, Suzhou 215000, Peoples R China 5.Soochow Univ, State Key Lab Radiat Med & Protect, Suzhou 215123, Peoples R China 6.Suzhou Bright Scistar Antibody Biotech Co Ltd, Block 7,17 ChangPing Rd, Suzhou 215152, Peoples R China 7.Soochow Univ, Affiliated Hosp 1, Dept Clin Pharmacol, 899 Pinghai Rd, Suzhou 215006, Peoples R China |
第一作者单位 | 免疫化学研究所; 生命科学与技术学院 |
通讯作者单位 | 免疫化学研究所; 生命科学与技术学院 |
第一作者的第一单位 | 免疫化学研究所 |
推荐引用方式 GB/T 7714 | Mao, Yurong,Wei, Ding,Fu, Fengqing,et al. Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,257. |
APA | Mao, Yurong.,Wei, Ding.,Fu, Fengqing.,Wang, Huihui.,Sun, Ziyu.,...&Chen, Hongli.(2023).Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,257. |
MLA | Mao, Yurong,et al."Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 257(2023). |
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