Evidence map›Paper›PMID 31416167›Full record

ArticleCancers2019

Incorporation of a Hydrophilic Spacer Reduces Hepatic Uptake of HER2-Targeting Affibody-DM1 Drug Conjugates.

Haozhong Ding, Mohamed Altai, Sara S Rinne, Anzhelika Vorobyeva, Vladimir Tolmachev, Torbjörn Gräslund, Anna Orlova

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 23 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Haozhong DingDepartment of Protein Science, KTH Royal Institute of Technology, Roslagstullsbacken 21, 114 17 Stockholm, Sweden.ORCID 0000-0003-1093-8222
Mohamed AltaiDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
Sara S RinneDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden.
Anzhelika VorobyevaDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
Vladimir TolmachevDepartment of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.ORCID 0000-0002-6122-1734
Torbjörn GräslundDepartment of Protein Science, KTH Royal Institute of Technology, Roslagstullsbacken 21, 114 17 Stockholm, Sweden.
Anna OrlovaDepartment of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden. Anna.orlova@ilk.uu.se.ORCID 0000-0001-6120-2683
Uppsala University · SEKTH Royal Institute of Technology · SE

Funding

Cancerfonden 2018/824Cancerfonden CAN2015/350Cancerfonden CAN 2017/425Vetenskapsrådet 2015-02353Vetenskapsrådet 2015-02509VINNOVA 2016-04060VINNOVA 2019-00104
6 · The paper itself

Abstract

Affibody molecules are small affinity-engineered scaffold proteins which can be engineered to bind to desired targets. The therapeutic potential of using an affibody molecule targeting HER2, fused to an albumin-binding domain (ABD) and conjugated with the cytotoxic maytansine derivate MC-DM1 (AffiDC), has been validated. Biodistribution studies in mice revealed an elevated hepatic uptake of the AffiDC, but histopathological examination of livers showed no major signs of toxicity. However, previous clinical experience with antibody drug conjugates have revealed a moderate- to high-grade hepatotoxicity in treated patients, which merits efforts to also minimize hepatic uptake of the AffiDCs. In this study, the aim was to reduce the hepatic uptake of AffiDCs and optimize their in vivo targeting properties. We have investigated if incorporation of hydrophilic glutamate-based spacers adjacent to MC-DM1 in the AffiDC, (Z

Indexed as

affibodyDM1drug conjugateshepatic uptake

Identifiers

PMID31416167
PMCPMC6721809
OpenAlexW2967084136

What OpenQuestion holds

Textmetadata
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.