Antibody-Drug Conjugates: Linking Cytotoxic Payloads to Monoclonal Antibodies

被引:474
作者
Ducry, Laurent [1 ]
Stump, Bernhard [1 ]
机构
[1] Lonza Ltd, CH-3930 Visp, Switzerland
关键词
ACUTE MYELOID-LEUKEMIA; TARGETED CANCER-THERAPY; ANTITUMOR-ACTIVITY; CALICHEAMICIN CONJUGATE; BIOLOGICAL EVALUATION; SELECTIVE TREATMENT; ANTIBIOTIC CC-1065; LINKER STABILITY; IN-VIVO; POTENT;
D O I
10.1021/bc9002019
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies (mAbs) with the potency of cytotoxic molecules, thereby taking advantage of the best characteristics of both components. Along with the development of the mAbs and cytotoxins, the design of chemical linkers to covalently bind these building blocks is making rapid progress but remains challenging. Recent advances have resulted in linkers having increased stability in the bloodstream while allowing efficient payload release within the tumor cell.
引用
收藏
页码:5 / 13
页数:9
相关论文
共 51 条
[41]   Selective treatment of cancer: Synthesis, biological evaluation and structural elucidation of novel analogues of the antibiotic CC-1065 and the duocarmycins [J].
Tietze, Lutz F. ;
Major, Felix ;
Schuberth, Ingrid ;
Spiegl, Dirk A. ;
Krewer, Birgit ;
Maksimenka, Katja ;
Bringmann, Gerhard ;
Magull, Joerg .
CHEMISTRY-A EUROPEAN JOURNAL, 2007, 13 (16) :4396-4409
[42]   Protease-mediated fragmentation of p-amidobenzyl ethers:: A new strategy for the activation of anticancer prodrugs [J].
Toki, BE ;
Cerveny, CG ;
Wahl, AF ;
Senter, PD .
JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (06) :1866-1872
[43]   CURE OF XENOGRAFTED HUMAN CARCINOMAS BY BR96-DOXORUBICIN IMMUNOCONJUGATES [J].
TRAIL, PA ;
WILLNER, D ;
LASCH, SJ ;
HENDERSON, AJ ;
HOFSTEAD, S ;
CASAZZA, AM ;
FIRESTONE, RA ;
HELLSTROM, I ;
HELLSTROM, KE .
SCIENCE, 1993, 261 (5118) :212-215
[44]   Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells [J].
van der Velden, VHJ ;
te Mervelde, JG ;
Hoogeveen, PG ;
Bernstein, ID ;
Houtsmuller, AB ;
Berger, MS ;
van Dongen, JJM .
BLOOD, 2001, 97 (10) :3197-3204
[45]  
VOGEL CL, 2009, J CLIN ONCOL S, V27, pS15
[46]   Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue [J].
Wang, Yuqiang ;
Li, Lianfa ;
Tian, Zhiming ;
Jiang, Wei ;
Larrick, James W. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (23) :7854-7861
[47]   Semisynthetic maytansine analogues for the targeted treatment of cancer [J].
Widdison, Wayne C. ;
Wilhelm, Sharon D. ;
Cavanagh, Emily E. ;
Whiteman, Kathleen R. ;
Leece, Barbara A. ;
Kovtun, Yelena ;
Goldmacher, Victor S. ;
Xie, Hongsheng ;
Steeves, Rita M. ;
Lutz, Robert J. ;
Zhao, Robert ;
Wang, Lintao ;
Blattler, Walter A. ;
Chari, Ravi V. J. .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (14) :4392-4408
[48]   Arming antibodies: prospects and challenges for immunoconjugates [J].
Wu, AM ;
Senter, PD .
NATURE BIOTECHNOLOGY, 2005, 23 (09) :1137-1146
[49]   Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice [J].
Xie, HS ;
Audette, C ;
Hoffee, M ;
Lambert, JM ;
Blättler, WA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2004, 308 (03) :1073-1082
[50]   Antibodies for targeted cancer therapy - Technical aspects and clinical perspectives [J].
Zangemeister-Wittke, U .
PATHOBIOLOGY, 2005, 72 (06) :279-286