Evidence map›Paper›PMID 25760770›Full record

ArticlemAbs2015

Phage display-based generation of novel internalizing antibody fragments for immunotoxin-based treatment of acute myeloid leukemia.

Jenny Fitting, Tobias Blume, Andre Ten Haaf, Wolfgang Blau, Stefan Gattenlöhner, Mehmet Kemal Tur, Stefan Barth

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.7field-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

11 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 4 institutions in 3 countries.

Jenny Fittinga Department of Experimental Medicine and Immunotherapy; Institute of Applied Medical Engineering; Helmholtz-Institute for Biomedical Engineering ; University Hospital RWTH Aachen ; Aachen , Germany.
Tobias Blume
Andre Ten Haaf
Wolfgang Blau
Stefan Gattenlöhner
Mehmet Kemal Tur
Stefan Barth
University of Giessen · DERWTH Aachen University · DEInstitute for Biomedical Engineering · CHTaipei Institute of Pathology · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The current standard treatment for acute myeloid leukemia (AML) is chemotherapy based on cytarabine and daunorubicine (7 + 3), but it discriminates poorly between malignant and benign cells. Dose-limiting off‑target effects and intrinsic drug resistance result in the inefficient eradication of leukemic blast cells and their survival beyond remission. This minimal residual disease is the major cause of relapse and is responsible for a 5-year survival rate of only 24%. More specific and efficient approaches are therefore required to eradicate malignant cells while leaving healthy cells unaffected. In this study, we generated scFv antibodies that bind specifically to the surface of AML blast cells and AML bone marrow biopsy specimens. We isolated the antibodies by phage display, using subtractive whole-cell panning with AML M2‑derived Kasumi‑1 cells. By selecting for internalizing scFv antibody fragments, we focused on potentially novel agents for intracellular drug delivery and tumor modulation. Two independent methods showed that 4 binders were internalized by Kasumi-1 cells. Furthermore, we observed the AML‑selective inhibition of cell proliferation and the induction of apoptosis by a recombinant immunotoxin comprising one scFv fused to a truncated form of Pseudomonas exotoxin A (ETA'). This method may therefore be useful for the selection of novel disease-specific internalizing antibody fragments, providing a novel immunotherapeutic strategy for the treatment of AML patients.

Indexed as

ADP Ribose TransferasesAntibodies, NeoplasmBacterial ToxinsExotoxinsImmunotoxinsSingle-Chain AntibodiesVirulence FactorsAntibody SpecificityBlast CrisisCell Line, TumorHumansLeukemia, Myeloid, AcutePseudomonas aeruginosa Exotoxin AADP Ribose TransferasesAntibodies, NeoplasmBacterial ToxinsExotoxinsImmunotoxinsPseudomonas aeruginosa Exotoxin ASingle-Chain AntibodiesVirulence Factorsacute myeloid leukemiaAML, acute myeloid leukemiaAML immunohistochemistryanti-AML antibody fragmentsCDR, Complementarity Determining RegionETA, Pseudomonas exotoxin Ainternalizing phage antibodiesin vitro efficacyPBMC, peripheral blood mononuclear cellphage display technologyprimary AML blast cellsrecombinant immunotoxinscFv, single chain variable fragment

Identifiers

PMID25760770
PMCPMC4622674
OpenAlexW1690893451

What OpenQuestion holds

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Registered trials

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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.