Recent advances in the construction of antibody-drug conjugates

被引：16

作者：

Chudasama, Vijay ^{[1
]}

Maruani, Antoine ^{[1
]}

Caddick, Stephen ^{[1
]}

机构：

[1] UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England

来源：

NATURE CHEMISTRY | 2016年 / 8卷 / 02期

基金：

英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

MICROBIAL TRANSGLUTAMINASE; TRASTUZUMAB EMTANSINE; BRENTUXIMAB VEDOTIN; CYSTEINE RESIDUES; ALDEHYDE TAG; AMINO-ACIDS; SITE; CANCER; STABILITY; ENABLES;

D O I：

10.1038/NCHEM.2415

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

引用

页码：113 / 118

页数：6

共 51 条

[1] Synthesis of site-specific antibody-drug conjugates using unnatural amino acids [J].

Axup, Jun Y. ;

Bajjuri, Krishna M. ;

Ritland, Melissa ;

Hutchins, Benjamin M. ;

Kim, Chan Hyuk ;

Kazane, Stephanie A. ;

Halder, Rajkumar ;

Forsyth, Jane S. ;

Santidrian, Antonio F. ;

Stafin, Karin ;

Lu, Yingchun ;

Hon Tran ;

Seller, Aaron J. ;

Biroce, Sandra L. ;

Szydlik, Aga ;

Pinkstaff, Jason K. ;

Tian, Feng ;

Sinha, Subhash C. ;

Felding-Habermann, Brunhilde ;

Smider, Vaughn V. ;

Schultz, Peter G. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (40) :16101-16106

[2] Bridging Disulfides for Stable and Defined Antibody Drug Conjugates [J].

Badescu, George ;

Bryant, Penny ;

Bird, Matthew ;

Henseleit, Korinna ;

Swierkosz, Julia ;

Parekh, Vimal ;

Tommasi, Rita ;

Pawlisz, Estera ;

Jurlewicz, Kosma ;

Farys, Monika ;

Camper, Nicolas ;

Sheng, XiaoBo ;

Fisher, Martin ;

Grygorash, Ruslan ;

Kyle, Andrew ;

Abhilash, Amrita ;

Frigerio, Mark ;

Edwards, Jeff ;

Godwin, Antony .

BIOCONJUGATE CHEMISTRY, 2014, 25 (06) :1124-1136

[3] Investigation into Temperature-Induced Aggregation of an Antibody Drug Conjugate [J].

Beckley, Nia S. ;

Lazzareschi, Kathlyn P. ;

Chih, Hung-Wei ;

Sharma, Vikas K. ;

Flores, Heather L. .

BIOCONJUGATE CHEMISTRY, 2013, 24 (10) :1674-1683

[4] Development of potent monoclonal antibody auristatin conjugates for cancer therapy [J].

Doronina, SO ;

Toki, BE ;

Torgov, MY ;

Mendelsohn, BA ;

Cerveny, CG ;

Chace, DF ;

DeBlanc, RL ;

Gearing, RP ;

Bovee, TD ;

Siegall, CB ;

Francisco, JA ;

Wahl, AF ;

Meyer, DL ;

Senter, PD .

NATURE BIOTECHNOLOGY, 2003, 21 (07) :778-784

[5] Aldehyde Tag Coupled with HIPS Chemistry Enables the Production of ADCs Conjugated Site-Specifically to Different Antibody Regions with Distinct in Vivo Efficacy and PK Outcomes [J].

Drake, Penelope M. ;

Albers, Aaron E. ;

Baker, Jeanne ;

Banas, Stefanie ;

Barfield, Robyn M. ;

Bhat, Abhijit S. ;

de Hart, Gregory W. ;

Garofalo, Albert W. ;

Holder, Patrick ;

Jones, Lesley C. ;

Kudirka, Romas ;

McFarland, Jesse ;

Zmolek, Wes ;

Rabuka, David .

BIOCONJUGATE CHEMISTRY, 2014, 25 (07) :1331-1341

[6]

Ehrlich P, 1913, Br Med J, V2, P353

[7] LOCALIZATION AND TOXICITY STUDY OF A VINDESINE-ANTI-CEA CONJUGATE IN PATIENTS WITH ADVANCED CANCER [J].

FORD, CHJ ;

NEWMAN, CE ;

JOHNSON, JR ;

WOODHOUSE, CS ;

REEDER, TA ;

ROWLAND, GF ;

SIMMONDS, RG .

BRITISH JOURNAL OF CANCER, 1983, 47 (01) :35-42

[8]

GHOSE T, 1972, CANCER, V29, P1398, DOI 10.1002/1097-0142(197205)29:5<1398::AID-CNCR2820290542>3.0.CO

[9]

2-D

[10] TRANSGLUTAMINASES - MULTIFUNCTIONAL CROSS-LINKING ENZYMES THAT STABILIZE TISSUES [J].

GREENBERG, CS ;

BIRCKBICHLER, PJ ;

RICE, RH .

FASEB JOURNAL, 1991, 5 (15) :3071-3077

← 1 2 3 4 5 6 →