Evidence map›Paper›PMID 25899161›Full record

ArticleJournal of cancer research and clinical oncology2015

Novel EGFR-specific immunotoxins based on panitumumab and cetuximab show in vitro and ex vivo activity against different tumor entities.

Judith Niesen, Christoph Stein, Hannes Brehm, Grit Hehmann-Titt, Rolf Fendel, Georg Melmer, Rainer Fischer, Stefan Barth

Open access · greenAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 50 citations in OpenAlex.

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  4. Enhanced cytotoxicity of aFrontiers in pharmacology · 2023
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  9. Preparation of a novel EGFR specific immunotoxin and its efficacy of anti-colorectal cancer in vitro and in vivo.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
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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

8 authors at 3 institutions in 1 country.

Judith NiesenFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany. judith.niesen@ime.fraunhofer.de.
Christoph SteinFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Hannes BrehmDepartment of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, RWTH Aachen University Clinic, Aachen, Germany.
Grit Hehmann-TittPharmedartis GmbH, Aachen, Germany.
Rolf FendelFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Georg MelmerPharmedartis GmbH, Aachen, Germany.
Rainer FischerFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Stefan BarthFraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstrasse 6, 52074, Aachen, Germany.
Fraunhofer Institute for Molecular Biology and Applied Ecology · DERWTH Aachen University · DEFraunhofer Society · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. EGFR-specific monoclonal antibodies (mAbs), such as cetuximab and panitumumab, have been approved for the treatment of colorectal and head and neck cancer. To increase tissue penetration, we constructed single-chain fragment variable (scFv) antibodies derived from these mAbs and evaluated their potential for targeted cancer therapy. The resulting scFv-based EGFR-specific immunotoxins (ITs) combine target specificity of the full-size mAb with the cell-killing activity of a toxic effector domain, a truncated version of Pseudomonas exotoxin A (ETA').

methodsThe ITs and corresponding imaging probes were tested in vitro against four solid tumor entities (rhabdomyosarcoma, breast, prostate and pancreatic cancer). Specific binding and internalization of the ITs scFv2112-ETA' (from cetuximab) and scFv1711-ETA' (from panitumumab) were demonstrated by flow cytometry and for the scFv-SNAP-tag imaging probes by live cell imaging. Cytotoxic potential of the ITs was analyzed in cell viability and apoptosis assays. Binding of the ITs was proofed ex vivo on rhabdomyosarcoma, prostate and breast cancer formalin-fixed paraffin-embedded biopsies.

resultsBoth novel ITs showed significant pro-apoptotic and anti-proliferative effects toward the target cells, achieving IC50 values of 4 pM (high EGFR expression) to 460 pM (moderate EGFR expression). Additionally, rapid internalization and specific in vitro and ex vivo binding on patient tissue were confirmed.

conclusionsThese data demonstrate the potent therapeutic activity of two novel EGFR-specific ETA'-based ITs. Both molecules are promising candidates for further development toward clinical use in the treatment of various solid tumors to supplement the existing therapeutic regimes.

Indexed as

ADP Ribose TransferasesAntibodies, MonoclonalAntineoplastic AgentsApoptosisBacterial ToxinsBlotting, WesternCell ProliferationCetuximabErbB ReceptorsExotoxinsFlow CytometryHumansImmunologic FactorsImmunotoxinsNeoplasmsPanitumumabADP Ribose TransferasesAntibodies, MonoclonalAntineoplastic AgentsBacterial ToxinsCetuximabEGFR protein, humanErbB ReceptorsExotoxinsImmunologic FactorsImmunotoxinsPanitumumabPseudomonas aeruginosa Exotoxin ASingle-Chain AntibodiesVirulence FactorsCancer therapyEpidermal growth factor receptor (EGFR)Immunotoxin (IT)Pseudomonas exotoxin A (ETA′)Single-chain fragment variable (scFv)SNAP-tag

Identifiers

PMID25899161
PMCPMC11824141
OpenAlexW2078085435

What OpenQuestion holds

Textmetadata
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.