Evidence map›Paper›PMID 27064440›Full record

ArticlemAbs2016

An optimized antibody-single-chain TRAIL fusion protein for cancer therapy.

Martin Siegemund, Oliver Seifert, Maria Zarani, Tamara Džinić, Valentino De Leo, Doris Göttsch, Sabine Münkel, Meike Hutt, Klaus Pfizenmaier, Roland E Kontermann

Abstract read
In one paragraph

Article in mAbs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

  1. Review
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  6. Review
  7. TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy.Frontiers in molecular biosciences · 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

10 authors.

Martin Siegemunda Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.
Oliver Seiferta Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.
Maria Zarani
Tamara Džinić
Valentino De Leo
Doris Göttscha Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.
Sabine Münkela Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.
Meike Hutta Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.
Klaus Pfizenmaiera Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.
Roland E Kontermanna Institute of Cell Biology and Immunology, University of Stuttgart , Stuttgart , Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fusion proteins combining oligomeric assemblies of a genetically obtained single-chain (sc) variant of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with antibodies directed against tumor-associated antigens represent a promising strategy to overcome the limited therapeutic activity of conventional soluble TRAIL. To further improve the scTRAIL module in order to obtain a robust, thermostable molecule of high activity, we performed a comprehensive analysis of the minimal TNF homology domain (THD) and optimized linkers between the 3 TRAIL subunits constituting a scTRAIL. Through a stepwise mutagenesis of the N- and C-terminal region and the joining linker sequences, we generated bioactive scTRAIL molecules comprising a covalent linkage of the C-terminal Val280 and the N-terminal position 122 by only 2 amino acid residues in combination with conservative exchanges at positions 122 and 279. The increased thermal stability and solubility of such optimized scTRAIL molecules translated into increased bioactivity in the diabody-scTRAIL (Db-scTRAIL) format, exemplified here for an epidermal growth factor receptor-specific Db-scTRAIL. Additional modifications within the diabody linkers resulted in a fusion protein exerting high, target-dependent apoptosis induction in tumor cell lines in vitro and potent antitumor activity in vivo. Our results illustrate that protein engineering of scTRAIL and associated peptide linkers provides a promising strategy to develop antibody-scTRAIL fusion proteins as effective antitumor therapeutics.

Indexed as

AnimalsAntineoplastic AgentsHumansMiceNeoplasms, ExperimentalProtein StabilityRecombinant Fusion ProteinsSingle-Chain AntibodiesTNF-Related Apoptosis-Inducing LigandXenograft Model Antitumor AssaysAntineoplastic AgentsRecombinant Fusion ProteinsSingle-Chain AntibodiesTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanApo2LapoptosisdiabodyEGFR targetingmouse xenograftthermal stabilityTNF homology domainTRAIL

Identifiers

PMID27064440
PMCPMC4968136

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.