Antibody-drug conjugates for cancer

被引:504
作者
Chau, Cindy H. [1 ]
Steeg, Patricia S. [2 ,3 ]
Figg, William D. [1 ]
机构
[1] NCI, Mol Pharmacol Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA
[2] NCI, Womens Malignancies Branch, Ctr Canc Res, NIH, Frederick, MD 21701 USA
[3] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA
基金
美国国家卫生研究院;
关键词
METASTATIC BREAST-CANCER; ACUTE MYELOID-LEUKEMIA; RELAPSED HODGKIN LYMPHOMA; BRENTUXIMAB VEDOTIN; TRASTUZUMAB EMTANSINE; GEMTUZUMAB OZOGAMICIN; OPEN-LABEL; ADULT PATIENTS; FDA APPROVAL; INTRACELLULAR TRAFFICKING;
D O I
10.1016/S0140-6736(19)31774-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antibody-drug conjugates (ADCs) are immunoconjugates comprised of a monoclonal antibody tethered to a cytotoxic drug (known as the payload) via a chemical linker. The ADC is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. To date, five ADCs have received market approval and over 100 are being investigated in various stages of clinical development. In this Therapeutics paper, we review recent clinical experience with the approved ADCs and other promising late-stage candidates on the horizon, following an overview of the biology and chemistry of ADCs and how the individual components of an ADC (antibody [or target], linker and conjugation chemistry, and cytotoxic payload) influence its activity. We briefly discuss opportunities for enhancing ADC efficacy, drug resistance, and future perspectives for this novel antibody-based molecular platform, which has great potential to make a paradigm shift in cancer chemotherapy.
引用
收藏
页码:793 / 804
页数:12
相关论文
共 87 条
[1]   Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial [J].
Amadori, Sergio ;
Suciu, Stefan ;
Selleslag, Dominik ;
Aversa, Franco ;
Gaidano, Gianluca ;
Musso, Maurizio ;
Annino, Luciana ;
Venditti, Adriano ;
Voso, Maria Teresa ;
Mazzone, Carla ;
Magro, Domenico ;
De Fabritiis, Paolo ;
Muus, Petra ;
Alimena, Giuliana ;
Mancini, Marco ;
Hagemeijer, Anne ;
Paoloni, Francesca ;
Vignetti, Marco ;
Fazi, Paola ;
Meert, Liv ;
Ramadan, Safaa Mahmoud ;
Willemze, Roel ;
de Witte, Theo ;
Baron, Frederic .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (09) :972-+
[2]   FDA Approval: Ado-Trastuzumab Emtansine for the Treatment of Patients with HER2-Positive Metastatic Breast Cancer [J].
Amiri-Kordestani, Laleh ;
Blumenthal, Gideon M. ;
Xu, Qiang Casey ;
Zhang, Lijun ;
Tang, Shenghui W. ;
Ha, Linan ;
Weinberg, Wendy C. ;
Chi, Bo ;
Candau-Chacon, Reyes ;
Hughes, Patricia ;
Russell, Anne M. ;
Miksinski, Sarah Pope ;
Chen, Xiao Hong ;
McGuinn, W. David ;
Palmby, Todd ;
Schrieber, Sarah J. ;
Liu, Qi ;
Wang, Jian ;
Song, Pengfei ;
Mehrotra, Nitin ;
Skarupa, Lisa ;
Clouse, Kathleen ;
Al-Hakim, Ali ;
Sridhara, Rajeshwari ;
Ibrahim, Amna ;
Justice, Robert ;
Pazdur, Richard ;
Cortazar, Patricia .
CLINICAL CANCER RESEARCH, 2014, 20 (17) :4436-4441
[3]   Bispecific Antibodies and Antibody-Drug Conjugates (ADCs) Bridging HER2 and Prolactin Receptor Improve Efficacy of HER2 ADCs [J].
Andreev, Julian ;
Thambi, Nithya ;
Bay, Andres E. Perez ;
Delfino, Frank ;
Martin, Joel ;
Kelly, Marcus P. ;
Kirshner, Jessica R. ;
Rafique, Ashique ;
Kunz, Arthur ;
Nittoli, Thomas ;
MacDonald, Douglas ;
Daly, Christopher ;
Olson, William ;
Thurston, Gavin .
MOLECULAR CANCER THERAPEUTICS, 2017, 16 (04) :681-693
[4]   Maytansine-bearing antibody-drug conjugates induce in vitro hallmarks of immunogenic cell death selectively in antigen-positive target cells [J].
Bauzon, Maxine ;
Drake, Penelope M. ;
Barfield, Robyn M. ;
Cornali, Brandon M. ;
Rupniewski, Igor ;
Rabuka, David .
ONCOIMMUNOLOGY, 2019, 8 (04)
[5]   Strategies and challenges for the next generation of antibody drug conjugates [J].
Beck, Alain ;
Goetsch, Liliane ;
Dumontet, Charles ;
Corvaia, Nathalie .
NATURE REVIEWS DRUG DISCOVERY, 2017, 16 (05) :315-337
[6]   Methods for site-specific drug conjugation to antibodies [J].
Behrens, Christopher R. ;
Liu, Bin .
MABS, 2014, 6 (01) :46-53
[7]   First FDA Approval of Dual Anti-HER2 Regimen: Pertuzumab in Combination with Trastuzumab and Docetaxel for HER2-Positive Metastatic Breast Cancer [J].
Blumenthal, Gideon M. ;
Scher, Nancy S. ;
Cortazar, Patricia ;
Chattopadhyay, Somesh ;
Tang, Shenghui ;
Song, Pengfei ;
Liu, Qi ;
Ringgold, Kimberly ;
Pilaro, Anne M. ;
Tilley, Amy ;
King, Kathryn E. ;
Graham, Laurie ;
Rellahan, Barbara L. ;
Weinberg, Wendy C. ;
Chi, Bo ;
Thomas, Colleen ;
Hughes, Patricia ;
Ibrahim, Amna ;
Justice, Robert ;
Pazdur, Richard .
CLINICAL CANCER RESEARCH, 2013, 19 (18) :4911-4916
[8]  
Bross PF, 2001, CLIN CANCER RES, V7, P1490
[9]   Next generation antibody drugs: pursuit of the 'high-hanging fruit' [J].
Carter, Paul J. ;
Lazar, Greg A. .
NATURE REVIEWS DRUG DISCOVERY, 2018, 17 (03) :197-223
[10]   Potent antibody therapeutics by design [J].
Carter, PJ .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (05) :343-357