Expanding the Reach of Antibody-Drug Conjugates

被引:47
作者
Chari, Ravi V. J. [1 ]
机构
[1] ImmunoGen Inc, 830 Winter St, Waltham, MA 02451 USA
关键词
CANCER-THERAPY;
D O I
10.1021/acsmedchemlett.6b00312
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Antibody-drug conjugates (ADCs) represent an emerging new paradigm in cancer therapy. The approval of two ADCs has spurred considerable interest in this area of research, and over 55 ADCs are currently in clinical testing. In order to improve the clinical success rate of ADC therapy, all three components of the ADC: the antibody, linker, and payload have to be optimized. While considerable improvements have been made in antibody properties and target selection, medicinal chemistry efforts have lagged behind, and there is a significant need for innovation in linker design and payloads.
引用
收藏
页码:974 / 976
页数:3
相关论文
共 12 条
[1]   Site-Specific Antibody-Drug Conjugates: The Nexus of Biciorthogonal Chemistry, Protein Engineering, and Drug Development [J].
Agarwal, Paresh ;
Bertozzi, Carolyn R. .
BIOCONJUGATE CHEMISTRY, 2015, 26 (02) :176-192
[2]   Targeted cancer therapy: Conferring specificity to cytotoxic drugs [J].
Chari, Ravi V. J. .
ACCOUNTS OF CHEMICAL RESEARCH, 2008, 41 (01) :98-107
[3]   Antibody- Drug Conjugates: An Emerging Concept in Cancer Therapy [J].
Chari, Ravi V. J. ;
Miller, Michael L. ;
Widdison, Wayne C. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2014, 53 (15) :3796-3827
[4]  
Donaghy H, 2016, COMMUNICATION
[5]   Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index [J].
Junutula, Jagath R. ;
Raab, Helga ;
Clark, Suzanna ;
Bhakta, Sunil ;
Leipold, Douglas D. ;
Weir, Sylvia ;
Chen, Yvonne ;
Simpson, Michelle ;
Tsai, Siao Ping ;
Dennis, Mark S. ;
Lu, Yanmei ;
Meng, Y. Gloria ;
Ng, Carl ;
Yang, Jihong ;
Lee, Chien C. ;
Duenas, Eileen ;
Gorrell, Jeffrey ;
Katta, Viswanatham ;
Kim, Amy ;
McDorman, Kevin ;
Flagella, Kelly ;
Venook, Rayna ;
Ross, Sarajane ;
Spencer, Susan D. ;
Wong, Wai Lee ;
Lowman, Henry B. ;
Vandlen, Richard ;
Sliwkowski, Mark X. ;
Scheller, Richard H. ;
Polakis, Paul ;
Mallet, William .
NATURE BIOTECHNOLOGY, 2008, 26 (08) :925-932
[6]   Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer [J].
Krop, Ian E. ;
Beeram, Muralidhar ;
Modi, Shanu ;
Jones, Suzanne F. ;
Holden, Scott N. ;
Yu, Wei ;
Girish, Sandhya ;
Tibbitts, Jay ;
Yi, Joo-Hee ;
Sliwkowski, Mark X. ;
Jacobson, Fred ;
Lutzker, Stuart G. ;
Burris, Howard A. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (16) :2698-2704
[7]   ABiparatopic HER2-Targeting Antibody-Drug Conjugate Induces Tumor Regression in Primary Models Refractory to or Ineligible for HER2-Targeted Therapy [J].
Li, John Y. ;
Perry, Samuel R. ;
Muniz-Medina, Vanessa ;
Wang, Xinzhong ;
Wetzel, Leslie K. ;
Rebelatto, Marlon C. ;
Hinrichs, Mary Jane Masson ;
Bezabeh, Binyam Z. ;
Fleming, Ryan L. ;
Dimasi, Nazzareno ;
Feng, Hui ;
Toader, Dorin ;
Yuan, Andy Q. ;
Xu, Lan ;
Lin, Jia ;
Gao, Changshou ;
Wu, Herren ;
Dixit, Rakesh ;
Osbourn, Jane K. ;
Coats, Steven R. .
CANCER CELL, 2016, 29 (01) :117-129
[8]   Discovery of Cytotoxic Dolastatin 10 Analogues with N-Terminal Modifications [J].
Maderna, Andreas ;
Doroski, Matthew ;
Subramanyam, Chakrapani ;
Porte, Alexander ;
Leverett, Carolyn A. ;
Vetelino, Beth C. ;
Chen, Zecheng ;
Risley, Hud ;
Parris, Kevin ;
Pandit, Jayvardhan ;
Varghese, Alison H. ;
Shanker, Suman ;
Song, Cynthia ;
Sukuru, Sai Chetan K. ;
Farley, Kathleen A. ;
Wagenaar, Melissa M. ;
Shapiro, Michael J. ;
Musto, Sylvia ;
Lam, My-Hanh ;
Loganzo, Frank ;
O'Donnell, Christopher J. .
JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (24) :10527-10543
[9]   A New Class of Antibody-Drug Conjugates with Potent DNA Alkylating Activity [J].
Miller, Michael L. ;
Fishkin, Nathan E. ;
Li, Wei ;
Whiteman, Kathleen R. ;
Kovtun, Yelena ;
Reid, Emily E. ;
Archer, Katie E. ;
Maloney, Erin K. ;
Audette, Charlene A. ;
Mayo, Michele F. ;
Wilhelm, Alan ;
Modafferi, Holly A. ;
Singh, Rajeeva ;
Pinkas, Jan ;
Goldmacher, Victor ;
Lambert, John M. ;
Chari, Ravi V. J. .
MOLECULAR CANCER THERAPEUTICS, 2016, 15 (08) :1870-1878
[10]   Natural Product Splicing Inhibitors: A New Class of Antibody-Drug Conjugate (ADC) Payloads [J].
Puthenveetil, Sujiet ;
Loganzo, Frank ;
He, Haiyin ;
Dirico, Ken ;
Green, Michael ;
Teske, Jesse ;
Musto, Sylvia ;
Clark, Tracey ;
Rago, Brian ;
Koehn, Frank ;
Veneziale, Robert ;
Falahaptisheh, Hadi ;
Han, Xiaogang ;
Barletta, Frank ;
Lucas, Judy ;
Subramanyam, Chakrapani ;
O'Donnell, Christopher J. ;
Tumey, L. Nathan ;
Sapra, Puja ;
Gerber, Hans Peter ;
Ma, Dangshe ;
Graziani, Edmund I. .
BIOCONJUGATE CHEMISTRY, 2016, 27 (08) :1880-1888