Evidence map›Paper›PMID 36743041›Full record

ArticleACS omega2023

Click Chemistry-Generated Auristatin F-Linker-Benzylguanine for a SNAP-Tag-Based Recombinant Antibody-Drug Conjugate Demonstrating Selective Cytotoxicity toward EGFR-Overexpressing Tumor Cells.

Allan M Huysamen, Olaolu E Fadeyi, Grace Mayuni, Dennis M Dogbey, Neelakshi Mungra, Fleury A N Biteghe, Natasha Hardcastle, Dharanidharan Ramamurthy, Olusiji A Akinrinmade, Krupa Naran and 5 more

Open access · goldAbstract read
In one paragraph

Article in ACS omega, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

7 citing papers in PubMed, 11 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

15 authors at 4 institutions in 2 countries.

Allan M HuysamenDepartment of Chemistry, University of Cape Town, PD Hahn Building, Cape Town 7700, South Africa.ORCID https://orcid.org/0000-0003-3170-0555
Olaolu E FadeyiDepartment of Chemistry, University of Cape Town, PD Hahn Building, Cape Town 7700, South Africa.
Grace MayuniMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Dennis M DogbeyMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Neelakshi MungraMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.ORCID https://orcid.org/0000-0002-5993-3943
Fleury A N BitegheDepartment of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, Los Angeles, California 90048, United States.
Natasha HardcastleMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Dharanidharan RamamurthyMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Olusiji A AkinrinmadeMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Krupa NaranMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.
Susan CooperDivision of Physiological Sciences, Department of Human Biology, University of Cape Town, Cape Town 7700, South Africa.
Dirk LangDivision of Physiological Sciences, Department of Human Biology, University of Cape Town, Cape Town 7700, South Africa.
Wolfgang RichterTUBE Pharmaceuticals, 1110 Wien, Austria.
Roger HunterDepartment of Chemistry, University of Cape Town, PD Hahn Building, Cape Town 7700, South Africa.ORCID https://orcid.org/0000-0001-8775-083X
Stefan BarthMedical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa.ORCID https://orcid.org/0000-0001-9589-653X
University of Cape Town · ZAAlbert Einstein College of Medicine · USCedars-Sinai Medical Center · USSeattle Children's Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) are bifunctional molecules combining the targeting potential of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs. This simple yet intelligently designed system directly addresses the lack of specificity encountered with conventional anti-cancer treatment regimes. However, despite their initial success, the generation of clinically sustainable and effective ADCs has been plagued by poor tumor penetration, undefined chemical linkages, unpredictable pharmacokinetic profiles, and heterogeneous mixtures of products. To this end, we generated a SNAP-tag-based fusion protein targeting the epidermal growth factor receptor (EGFR)-a biomarker of aggressive and drug-resistant cancers. Here, we demonstrate the use of a novel click coupling strategy to engineer a benzylguanine (BG)-linker-auristatin F (AuriF) piece that can be covalently tethered to the EGFR-targeting SNAP-tag-based fusion protein in an irreversible 1:1 stoichiometric reaction to form a homogeneous product. Furthermore, using these recombinant ADCs to target EGFR-overexpressing tumor cells, we provide a proof-of-principle for generating biologically active antimitotic therapeutic proteins capable of inducing cell death in a dose-dependent manner, thus alleviating some of the challenges of early ADC development.

Identifiers

PMID36743041
PMCPMC9893251
OpenAlexW4317035097

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.