Advances in Antibody-Drug Conjugate Design: Current Clinical Landscape and Future Innovations

被引:51
作者
Gauzy-Lazo, Laurence [1 ]
Sassoon, Ingrid [2 ]
Brun, Marie-Priscille [3 ]
机构
[1] Sanofi, Emerging Chem Modal, 1 Ave Pierre Brossolette, F-91385 Chilly Mazarin, France
[2] Sanofi, Immunooncol Therapeut Area, Vitry Sur Seine, France
[3] Sanofi, Emerging Chem Modal, Vitry Sur Seine, France
关键词
antibody-drug conjugate; cytotoxic payload; site-specific conjugation; alternative formats; SITE-SPECIFIC CONJUGATION; TRASTUZUMAB EMTANSINE T-DM1; TOPOISOMERASE-I INHIBITOR; MONOCLONAL-ANTIBODY; SACITUZUMAB GOVITECAN; ANTITUMOR-ACTIVITY; GEMTUZUMAB OZOGAMICIN; THERAPEUTIC INDEX; CANCER-THERAPY; PYRROLOBENZODIAZEPINE DIMER;
D O I
10.1177/2472555220912955
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The targeted delivery of potent cytotoxic molecules into cancer cells is considered a promising anticancer strategy. The design of clinically effective antibody-drug conjugates (ADCs), in which biologically active drugs are coupled through chemical linkers to monoclonal antibodies, has presented challenges for pharmaceutical researchers. After 30 years of intensive research and development activities, only seven ADCs have been approved for clinical use; two have received fast-track designation and two breakthrough therapy designation from the Food and Drug Administration. There is continued interest in the field, as documented by the growing number of candidates in clinical development. This review aims to summarize the most recent innovations that have been applied to the design of ADCs undergoing early- and late-stage clinical trials. Discovery and rational optimization of new payloads, chemical linkers, and antibody formats have improved the therapeutic index of next-generation ADCs, ultimately resulting in improved clinical benefit for the patients.
引用
收藏
页码:843 / 868
页数:26
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