Evidence map›Paper›PMID 34197861›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2021

Site-specific antibody-drug conjugates with variable drug-to-antibody-ratios for AML therapy.

Zhefu Dai, Xiao-Nan Zhang, Qinqin Cheng, Fan Fei, Tianling Hou, Jiawei Li, Alireza Abdolvahabi, Junji Watanabe, Hua Pei, Goar Smbatyan and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Synthesis of Bispecific Conjugates by ADP-Ribosyl Cyclases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Genetically reprogrammed exosomes for immunotherapy of acute myeloid leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. Article
  8. Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.Protein science : a publication of the Protein Society · 2024
    Article
  9. Article
  10. Rational design of humanized antibody inhibitors for cathepsin S.Archives of biochemistry and biophysics · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Zhefu DaiDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Xiao-Nan ZhangDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Qinqin ChengDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Fan FeiDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Tianling HouDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Jiawei LiDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Alireza AbdolvahabiMass Spectrometry Core Facility, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Junji WatanabeTranslational Research Laboratory, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Hua PeiTitus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Goar SmbatyanDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Jianming XieDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Stan G LouieTitus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
Yong ZhangDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA; Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA; Research Center for Liver Diseases, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: yongz@usc.edu.
University of Southern California · US

Funding

Chemistry and Biology of ADP-Ribosylation-Dependent SignalingR35GM137901 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Yong Zhang · 2020 to 2026
$2.5M
NIGMS NIH HHS R35 GM137901
6 · The paper itself

Abstract

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.

Indexed as

Antineoplastic AgentsImmunoconjugatesLeukemia, Myeloid, AcutePharmaceutical PreparationsAntibodies, MonoclonalHumansAntibodies, MonoclonalAntineoplastic AgentsImmunoconjugatesPharmaceutical PreparationsAcute myeloid leukemiaAntibody-drug conjugateProtein engineeringTargeted therapy

Identifiers

PMID34197861
PMCPMC8373670
OpenAlexW3176339725

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.