Antibody-drug conjugates: targeted drug delivery for cancer

被引:488
|
作者
Alley, Stephen C. [1 ]
Okeley, Nicole M. [1 ]
Senter, Peter D. [1 ]
机构
[1] Seattle Genet Inc, Bothell, WA 98021 USA
关键词
MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; LINKER STABILITY; THERAPY TARGET; CYTOTOXIC DRUG; BREAST-CANCER; POTENT; AURISTATIN; CHEMOTHERAPY; ANTIGEN;
D O I
10.1016/j.cbpa.2010.06.170
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The antibody-drug conjugate field has made significant progress recently owing to careful optimization of several parameters, including mAb specificity, drug potency, linker technology, and the stoichiometry and placement of conjugated drugs. The underlying reason for this has been obtained in pre-clinical biodistribution and pharmacokinetics studies showing that targeted delivery leads to high intratumoral free drug concentrations, while non-target tissues are largely spared from chemotherapeutic exposure. Recent developments in the field have led to an increase in the number of ADCs being tested clinically, with 3 in late stage clinical trials: brentuximab vedotin (also referred to as SGN-35) for Hodgkin lymphoma; Trastuzumab-DM1 for breast cancer; and Inotuzumab ozogamicin for non-Hodgkin lymphoma. This review highlights the recent pre-clinical and clinical advances that have been made.
引用
收藏
页码:529 / 537
页数:9
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