Evidence map›Paper›PMID 29062027›Full record

ArticleNature communications2017

Harnessing a catalytic lysine residue for the one-step preparation of homogeneous antibody-drug conjugates.

Alex R Nanna, Xiuling Li, Even Walseng, Lee Pedzisa, Rebecca S Goydel, David Hymel, Terrence R Burke, William R Roush, Christoph Rader

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

41 citing papers in PubMed, 90 citations in OpenAlex.

  1. Review
  2. Review
  3. Chemical Tagging ofJournal of the American Chemical Society · 2025
    Article
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  14. Review
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  17. Review
  18. Precision Modification of Native Antibodies.Bioconjugate chemistry · 2021
    Review
  19. Site-specific antibody-drug conjugates with variable drug-to-antibody-ratios for AML therapy.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Article
  20. 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

9 authors at 3 institutions in 1 country.

Alex R NannaDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Xiuling LiDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Even WalsengDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Lee PedzisaDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Rebecca S GoydelDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
David HymelChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
Terrence R BurkeChemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
William R RoushDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA. roush@scripps.edu.
Christoph RaderDepartment of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA. crader@scripps.edu.
Scripps Research Institute · USNational Cancer Institute · USNational Institutes of Health · US

Funding

Inhibitors of Tyrosine Kinase-Dependent Signalling as Anti-Cancer AgentsZIABC006198 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BURKE, TERRENCE · 2009 to 2025
$13.7M
Novel Enediyne-Based Antibody-Drug Conjugates for CancersR01CA204484 · NCI · UNIVERSITY OF FLORIDA · PI Natarajan Muthusamy, Ben Shen · 2017 to 2026
$4.6M
Chemically Programmed Bispecific Antibodies for Cancer TherapyR01CA181258 · NCI · SCRIPPS FLORIDA · PI RADER, CHRISTOPH · 2014 to 2018
$2.0M
A Drug Delivery Strategy for Targeted Therapy of Chronic Lymphocytic LeukemiaU01CA174844 · NCI · SCRIPPS FLORIDA · PI RADER, CHRISTOPH · 2013 to 2015
$1.4M
NCI NIH HHS R01 CA181258NCI NIH HHS R01 CA204484NCI NIH HHS U01 CA174844
6 · The paper itself

Abstract

Current strategies to produce homogeneous antibody-drug conjugates (ADCs) rely on mutations or inefficient conjugation chemistries. Here we present a strategy to produce site-specific ADCs using a highly reactive natural buried lysine embedded in a dual variable domain (DVD) format. This approach is mutation free and drug conjugation proceeds rapidly at neutral pH in a single step without removing any charges. The conjugation chemistry is highly robust, enabling the use of crude DVD for ADC preparation. In addition, this strategy affords the ability to precisely monitor the efficiency of drug conjugation with a catalytic assay. ADCs targeting HER2 were prepared and demonstrated to be highly potent and specific in vitro and in vivo. Furthermore, the modular DVD platform was used to prepare potent and specific ADCs targeting CD138 and CD79B, two clinically established targets overexpressed in multiple myeloma and non-Hodgkin lymphoma, respectively.

Indexed as

AnimalsAntineoplastic Agentsbeta-LactamsCatalysisCell Line, TumorChemistry, PharmaceuticalEpitopes, T-LymphocyteFemaleHumansHydrogen-Ion ConcentrationImmunoconjugatesK562 CellsLymphoma, Non-HodgkinLysineMiceMultiple MyelomaAntineoplastic Agentsbeta-LactamsEpitopes, T-LymphocyteImmunoconjugatesLysinePharmaceutical PreparationsSDC1 protein, humanSyndecan-1Trastuzumab

Identifiers

PMID29062027
PMCPMC5653646
OpenAlexW2765304871

What OpenQuestion holds

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LicenceCC BY
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.