Evidence map›Paper›PMID 34576184›Full record

ArticleInternational journal of molecular sciences2021

An Attenuated Targeted-TNF Localizes to Tumors In Vivo and Regains Activity at the Site of Disease.

Sheila Dakhel, Christian Lizak, Mattia Matasci, Jacqueline Mock, Alessandra Villa, Dario Neri, Samuele Cazzamalli

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 30% 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, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Antibody-drug conjugates come of age in oncology.Nature reviews. Drug discovery · 2023
    Review
  9. Review
  10. The present and future of immunocytokines for cancer treatment.Cellular and molecular life sciences : CMLS · 2022
    Review
  11. Review
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 2 countries.

Sheila DakhelPhilochem AG, CH-8112 Otelfingen, Switzerland.
Christian LizakPhilochem AG, CH-8112 Otelfingen, Switzerland.
Mattia MatasciPhilochem AG, CH-8112 Otelfingen, Switzerland.
Jacqueline MockPhilochem AG, CH-8112 Otelfingen, Switzerland.ORCID 0000-0002-4618-1113
Alessandra VillaPhilochem AG, CH-8112 Otelfingen, Switzerland.
Dario NeriPhilochem AG, CH-8112 Otelfingen, Switzerland.
Samuele CazzamalliPhilochem AG, CH-8112 Otelfingen, Switzerland.
Philochem (Switzerland) · CHPhilogen (Italy) · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-cytokine fusion proteins (immunocytokines) are gaining importance for cancer therapy, but those products are often limited by systemic toxicity related to the activity of the cytokine payload in circulation and in secondary lymphoid organs. Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. Here we describe a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. The fusion of the TNF(I97A) mutant to the L19 antibody promoted restoration of anti-tumor activity upon accumulation on the cognate antigen, the alternatively spliced EDB domain of fibronectin. In vivo administration of high doses (375 μg/Kg) of the fusion protein showed a potent anti-tumor effect without apparent toxicity compared with the wild type protein. L19-TNF

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCricetulusCytokinesFemaleFibronectinsFluorescent Antibody TechniqueImmunotherapyMiceMice, Inbred BALB CMutationProtein Structure, SecondaryReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor-alphaAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCytokinesFibronectinsReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor-alphaactivity-on-demandEDB-fibronectinimmunocytokinestargeted-tumor necrosis factortumor targeting

Identifiers

PMID34576184
PMCPMC8469155
OpenAlexW3200154404

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.