Site-specific conjugation improves therapeutic index of antibody drug conjugates with high drug loading

被引:116
|
作者
Strop, Pavel [1 ]
Delaria, Kathy [1 ]
Foletti, Davide [1 ]
Witt, Jody Melton [1 ]
Hasa-Moreno, Adela [1 ]
Poulsen, Kris [1 ]
Casas, Meritxell Galindo [1 ]
Dorywalska, Magdalena [1 ]
Farias, Santiago [1 ]
Pios, Ariel [1 ]
Lui, Victor [1 ]
Dushin, Russell [2 ]
Zhou, Dahui [2 ]
Navaratnain, Thayalan [2 ]
Trani, Thomas-Toan [1 ]
Sutton, Janette [1 ]
Lindquist, Kevin C. [1 ]
Han, Bora [3 ]
Litt, Shu-Hui [1 ]
Shelton, David L. [1 ]
Pons, Jaume [1 ]
Rajpal, Arvind [1 ]
机构
[1] Pfizer Inc, Rinat Labs, San Francisco, CA 94080 USA
[2] Pfizer Inc, Worldwide Med Chem, Groton, CT 06340 USA
[3] Pfizer Inc, Drug Safety Res & Dev, San Diego, CA USA
关键词
STABILITY;
D O I
10.1038/nbt.3274
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
引用
收藏
页码:694 / 696
页数:3
相关论文
共 50 条
  • [21] Design and Validation of Linkers for Site-Specific Preparation of Antibody-Drug Conjugates Carrying Multiple Drug Copies Per Cysteine Conjugation Site
    Kumar, Amit
    Mao, Shenlan
    Dimasi, Nazzareno
    Gao, Changshou
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (18) : 1 - 11
  • [22] Site-specific antibody-drug conjugates with variable drug-to-antibody-ratios for AML therapy
    Dai, Zhefu
    Zhang, Xiao-Nan
    Cheng, Qinqin
    Fei, Fan
    Hou, Tianling
    Li, Jiawei
    Abdolvahabi, Alireza
    Watanabe, Junji
    Pei, Hua
    Smbatyan, Goar
    Xie, Jianming
    Lenz, Heinz-Josef
    Louie, Stan G.
    Zhang, Yong
    JOURNAL OF CONTROLLED RELEASE, 2021, 336 : 433 - 442
  • [23] A site-specific approach to improved antibody-drug conjugates.
    Italia, James
    JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (15)
  • [24] Highly Potent, Anthracycline-based Antibody-Drug Conjugates Generated by Enzymatic, Site-specific Conjugation
    Stefan, Nikolas
    Gebleux, Remy
    Waldmeier, Lorenz
    Hell, Tamara
    Escher, Marie
    Wolter, Fabian I.
    Grawunder, Ulf
    Beerli, Roger R.
    MOLECULAR CANCER THERAPEUTICS, 2017, 16 (05) : 879 - 892
  • [25] Methods for site-specific drug conjugation to antibodies
    Behrens, Christopher R.
    Liu, Bin
    MABS, 2014, 6 (01) : 46 - 53
  • [26] Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates
    Ben-Quan Shen
    Keyang Xu
    Luna Liu
    Helga Raab
    Sunil Bhakta
    Margaret Kenrick
    Kathryn L Parsons-Reponte
    Janet Tien
    Shang-Fan Yu
    Elaine Mai
    Dongwei Li
    Jay Tibbitts
    Jakub Baudys
    Ola M Saad
    Suzie J Scales
    Paul J McDonald
    Philip E Hass
    Charles Eigenbrot
    Trung Nguyen
    Willy A Solis
    Reina N Fuji
    Kelly M Flagella
    Darshana Patel
    Susan D Spencer
    Leslie A Khawli
    Allen Ebens
    Wai Lee Wong
    Richard Vandlen
    Surinder Kaur
    Mark X Sliwkowski
    Richard H Scheller
    Paul Polakis
    Jagath R Junutula
    Nature Biotechnology, 2012, 30 : 184 - 189
  • [27] Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates
    Shen, Ben-Quan
    Xu, Keyang
    Liu, Luna
    Raab, Helga
    Bhakta, Sunil
    Kenrick, Margaret
    Parsons-Reponte, Kathryn L.
    Tien, Janet
    Yu, Shang-Fan
    Mai, Elaine
    Li, Dongwei
    Tibbitts, Jay
    Baudys, Jakub
    Saadi, Ola M.
    Scales, Suzie J.
    McDonald, Paul J.
    Hass, Philip E.
    Eigenbrot, Charles
    Trung Nguyen
    Solis, Willy A.
    Fuji, Reina N.
    Flagella, Kelly M.
    Patel, Darshana
    Spencer, Susan D.
    Khawlil, Leslie A.
    Ebens, Allen
    Wong, Wai Lee
    Vandlen, Richard
    Kaur, Surinder
    Sliwkowski, Mark X.
    Scheller, Richard H.
    Polakis, Paul
    Junutula, Jagath R.
    NATURE BIOTECHNOLOGY, 2012, 30 (02) : 184 - 189
  • [28] Site-Specific Trastuzumab Maytansinoid Antibody-Drug Conjugates with Improved Therapeutic Activity through Linker and Antibody Engineering
    Pillow, Thomas H.
    Tien, Janet
    Parsons-Reponte, Kathryn L.
    Bhakta, Sunil
    Li, Hao
    Staben, Leanna R.
    Li, Guangmin
    Chuh, Josefa
    Fourie-O'Donohue, Aimee
    Darwish, Martine
    Yip, Victor
    Liu, Luna
    Leipold, Douglas D.
    Su, Dian
    Wu, Elmer
    Spencer, Susan D.
    Shen, Ben-Quan
    Xu, Keyang
    Kozak, Katherine R.
    Raab, Helga
    Vandlen, Richard
    Phillips, Gail D. Lewis
    Scheller, Richard H.
    Polakis, Paul
    Sliwkowski, Mark X.
    Flygare, John A.
    Junutula, Jagath R.
    JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (19) : 7890 - 7899
  • [29] Site-Specific Conjugation Strategy for Dual Antibody-Drug Conjugates Using Aerobic Formylglycine-Generating Enzymes
    Boschanski, Mareile
    Krueger, Tobias
    Karsten, Lennard
    Falck, Georg
    Alam, Sarfaraz
    Gerlach, Marcus
    Mueller, Benjamin
    Mueller, Kristian M.
    Sewald, Norbert
    Dierks, Thomas
    BIOCONJUGATE CHEMISTRY, 2021, 32 (06) : 1167 - 1174
  • [30] Antibody-drug conjugates: engineered N-terminal serine residues as a novel approach for site-specific conjugation
    Tavares, Daniel
    Rui, Lingyun
    Ab, Olga
    Harris, Luke
    Maloney, Erin
    Keating, Thomas
    Chittenden, Thomas
    Fishkin, Nathan
    CANCER RESEARCH, 2015, 75