Antibody-drug conjugates: Basic concepts, examples and future perspectives

被引:152
作者
Casi, Giulio [2 ]
Neri, Dario [1 ]
机构
[1] ETH, Swiss Fed Inst Technol, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland
[2] Philochem AG, CH-8112 Otelfingen, Switzerland
关键词
Antibody-drug conjugates; Non-internalizing monoclonal antibodies; Traceless linkers; SENSITIVE DIPEPTIDE PRODRUGS; HER2-POSITIVE BREAST-CANCER; ACUTE MYELOID-LEUKEMIA; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; CALICHEAMICIN CONJUGATE; TARGETED CHEMOTHERAPY; GEMTUZUMAB OZOGAMICIN; TUMOR VASCULATURE; CYTOTOXIC DRUG;
D O I
10.1016/j.jconrel.2012.01.026
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Conventional anticancer therapeutics often suffer from lack of specificity, resulting in poor therapeutic indexes and substantial toxicities to normal healthy tissues. Monoclonal antibodies have demonstrated considerable utility in cancer medicine, but their curative potential is often limited. Antibody-drug conjugates represent an innovative therapeutic approach that combines the desirable properties of monoclonal antibodies, with the cell killing activity of cytotoxic drugs, reducing systemic toxicity and increasing the therapeutic benefit for patients. In this review, we outline prominent examples of early and recent antibody-drug conjugates, discussing drugs, linker chemistries and classes of targets for product development. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:422 / 428
页数:7
相关论文
共 60 条
[1]   Antibody-drug conjugates: targeted drug delivery for cancer [J].
Alley, Stephen C. ;
Okeley, Nicole M. ;
Senter, Peter D. .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2010, 14 (04) :529-537
[2]   A Traceless Vascular-Targeting Antibody-Drug Conjugate for Cancer Therapy [J].
Bernardes, Goncalo J. L. ;
Casi, Giulio ;
Truessel, Sabrina ;
Hartmann, Isabelle ;
Schwager, Kathrin ;
Scheuermann, Joerg ;
Neri, Dario .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (04) :941-944
[3]   Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C [J].
Brack, Simon S. ;
Silacci, Michela ;
Birchler, Manfred ;
Neri, Dario .
CLINICAL CANCER RESEARCH, 2006, 12 (10) :3200-3208
[4]  
BRASLAWSKY GR, 1990, CANCER RES, V50, P6608
[5]  
Bross PF, 2001, CLIN CANCER RES, V7, P1490
[6]   Potent antibody therapeutics by design [J].
Carter, PJ .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (05) :343-357
[7]  
Casi G., 2010, PCT/EP2011/004664, Patent No. 2011004664
[8]   Recent developments in the maytansinoid antitumor agents [J].
Cassady, JM ;
Chan, KK ;
Floss, HG ;
Leistner, E .
CHEMICAL & PHARMACEUTICAL BULLETIN, 2004, 52 (01) :1-26
[9]   A chemical proteomics approach for the identification of accessible antigens expressed in human kidney cancer [J].
Castronovo, Vincent ;
Waltregny, David ;
Kischel, Philippe ;
Roesli, Christoph ;
Elia, Giuliano ;
Rybak, Jascha-N. ;
Neri, Dario .
MOLECULAR & CELLULAR PROTEOMICS, 2006, 5 (11) :2083-2091
[10]   Targeted cancer therapy: Conferring specificity to cytotoxic drugs [J].
Chari, Ravi V. J. .
ACCOUNTS OF CHEMICAL RESEARCH, 2008, 41 (01) :98-107