Evidence map›Paper›PMID 23887603›Full record

ArticleBritish journal of cancer2013

The antibody-based targeted delivery of TNF in combination with doxorubicin eradicates sarcomas in mice and confers protective immunity.

T Hemmerle, P Probst, L Giovannoni, A J Green, T Meyer, D Neri

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

54 citing papers in PubMed, 96 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

6 authors at 4 institutions in 3 countries.

T HemmerleDepartment of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.
P Probst
L Giovannoni
A J Green
T Meyer
D Neri
CRUK Lung Cancer Centre of Excellence · GBETH Zurich · CHÉcole Polytechnique Fédérale de Lausanne · CHPhilogen (Italy) · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSoft-tissue sarcomas are a group of malignancies of mesenchymal origin, which typically have a dismal prognosis if they reach the metastatic stage. The observation of rare spontaneous remissions in patients suffering from concomitant bacterial infections had triggered the clinical investigation of the use of heat-killed bacteria as therapeutic agents (Coley's toxin), which induced complete responses in patients in the pre-chemotherapy era and is now known to mediate substantial elevations in serum TNF levels.

methodsWe designed and developed a novel immunocytokine based on murine TNF sequentially fused to the antibody fragment F8 (specific to extra-domain A of fibronectin). The antitumor activity was studied in two syngeneic murine sarcoma models.

resultsThe L19 antibody (specific to extra-domain B of fibronectin) has shown by SPECT imaging procedures to selectively localise on sarcoma in a patient with a peripheral nerve sheath tumour, and immunohistochemical analysis of human soft-tissue sarcoma samples showed comparable antigen expression of EDA and EDB. The antibody-based pharmacodelivery of TNF by the fusion protein 'F8-TNF' to oncofetal fibronectin in sarcoma-bearing mice leads to complete and long-lasting tumour eradications when administered in combination with doxorubicin, the first-line drug for the treatment of sarcomas in humans. Doxorubicin alone did not display any therapeutic effect in both tested models of this study. The cured mice had acquired protective immunity against the tumour, as they rejected subsequent challenges with sarcoma cells.

conclusionThe findings of this study provide a rationale for the clinical study of the fully human immunocytokine L19-TNF in combination with doxorubicin in patients with soft-tissue sarcoma.

Indexed as

Drug Delivery SystemsAnimalsAntibiotics, AntineoplasticAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCell Line, TumorCHO CellsCricetulusDoxorubicinFemaleHumansMiceRecombinant Fusion ProteinsSarcomaTumor Necrosis FactorsAntibiotics, AntineoplasticAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDoxorubicinF8 monoclonal antibodyRecombinant Fusion ProteinsTumor Necrosis Factors

Identifiers

PMID23887603
PMCPMC3778281
OpenAlexW1994885924

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.