Site-specific antibody-drug conjugates with variable drug-to-antibody-ratios for AML therapy.
Site-specific antibody-drug conjugates with variable drug-to-antibody-ratios for AML therapy.
复制标题
用于AML治疗的具有可变药物与抗体比率的位点特异性抗体-药物缀合物。
DOI：
10.1016/j.jconrel.2021.06.041
复制
发表时间：
2021-08-10
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Dai Z;Zhang XN;Cheng Q;Fei F;Hou T;Li J;Abdolvahabi A;Watanabe J;Pei H;Smbatyan G;Xie J;Lenz HJ;Louie SG;Zhang Y
Random conjugations of chemotherapeutics to monoclonal antibodies result in heterogeneous antibody-drug conjugates (ADCs) with suboptimal pharmacological properties. We recently developed a new technology for facile generation of homogeneous ADCs by harnessing human CD38 catalytic domain and its dinucleotide-derived covalent inhibitor, termed ADP-ribosyl cyclase-enabled ADCs (ARC-ADCs). Herein we advance this technology by designing and synthesizing ARC-ADCs with customizable drug-to-antibody ratios (DARs). Through varying numbers and locations of CD38 fused to an antibody targeting human C-type lectin-like molecule-1 (hCLL-1), ARC-ADCs featuring DARs of 2 and 4 were rapidly generated via a single step with cytotoxic monomethyl auristatin F (MMAF) as payloads. In contrast to anti-hCLL-1 ARC-ADC carrying 2 drug molecules, anti-hCLL-1 ARC-ADC with a DAR of 4 shows highly potent activity in killing hCLL-1-positive acute myeloid leukemia (AML) cells both in vitro and in vivo. This work provides novel ADC candidates for combating AML and supports ARC-ADC as a general and versatile approach for producing site-specific ADCs with defined DARs.
登录
查看更多内容
DOI：
10.1016/j.nano.2019.04.007
发表时间：
2019-08
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
--
作者：
Lin TY;Zhu Y;Li Y;Zhang H;Ma AH;Long Q;Keck J;Lam KS;Pan CX;Jonas BA
通讯作者：
Jonas BA
影响因子：
4
作者：
Woitok M;Klose D;Di Fiore S;Richter W;Stein C;Gresch G;Grieger E;Barth S;Fischer R;Kolberg K;Niesen J
通讯作者：
Niesen J
影响因子：
7.5
作者：
Jiang, Ying-Ping;Liu, Bob Y.;Junutula, Jagath R.
通讯作者：
Junutula, Jagath R.
影响因子：
3.7
作者：
Beerli RR;Hell T;Merkel AS;Grawunder U
通讯作者：
Grawunder U
影响因子：
16.6
作者：
Lu, Hua;Zhou, Quan;Deshmukh, Vishal;Phull, Hardeep;Ma, Jennifer;Tardif, Virginie;Naik, Rahul R.;Bouvard, Claire;Zhang, Yong;Choi, Seihyun;Lawson, Brian R.;Zhu, Shoutian;Kim, Chan Hyuk;Schultz, Peter G.
通讯作者：
Schultz, Peter G.