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])
ISSN0223-5234
EISSN1768-3254
卷号257
发表状态已发表
DOI10.1016/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
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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
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
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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