Evidence map›Paper›PMID 26474755›Full record

ArticleJournal of experimental & clinical cancer research : CR2015

Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE®), is highly active against primary uterine and ovarian carcinosarcoma cell lines in vitro.

Francesca Ferrari, Stefania Bellone, Jonathan Black, Carlton L Schwab, Salvatore Lopez, Emiliano Cocco, Elena Bonazzoli, Federica Predolini, Gulden Menderes, Babak Litkouhi and 5 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
3.5field-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

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.

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  15. BiTE secretion from in situ-programmed myeloid cells results in tumor-retained pharmacology.Journal of controlled release : official journal of the Controlled Release Society · 2022
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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

15 authors at 1 institution in 1 country.

Francesca FerrariDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. francesca.ferrari@yale.edu.
Stefania BelloneDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. stefania.bellone@yale.edu.
Jonathan BlackDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. jonathan.black@yale.edu.
Carlton L SchwabDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. carlton.schwab@yale.edu.
Salvatore LopezDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. salvatore.lopez@yale.edu.
Emiliano CoccoDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. emiliano.cocco@yale.edu.
Elena BonazzoliDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. elena.bonazzoli@yale.edu.
Federica PredoliniDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. ferica.predolini@yale.edu.
Gulden MenderesDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. gulden.menderes@yale.edu.
Babak LitkouhiDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. babak.litkouhi@yale.edu.
Elena RatnerDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. elena.ratner@yale.edu.
Dan-Arin SilasiDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. dan-arin.silasi@yale.edu.
Masoud AzodiDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. masoud.azodi@yale.edu.
Peter E SchwartzDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. peter.shwartz@yale.edu.
Alessandro D SantinDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. alessandro.santin@yale.edu.
Yale University · US

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Integrated genomic analysis of racial disparities in endometrial cancerU01CA176067 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2014 to 2018
$1.7M
CPE Peptide-Based Nanoparticles for the Diagnosis and Therapy of Chemotherapy ResR01CA154460 · NCI · YALE UNIVERSITY · PI SANTIN, ALESSANDRO D · 2011 to 2015
$1.7M
NCI NIH HHS CA-16359NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA154460NCI NIH HHS R01 CA154460-01A1NCI NIH HHS U01 CA176067NCI NIH HHS U01 CA176067-01A1
6 · The paper itself

Abstract

backgroundUterine and ovarian carcinosarcomas (CS) are rare but highly aggressive gynecologic tumors which carry an extremely poor prognosis. We evaluated the expression levels of EpCAM and the in vitro activity of solitomab, a bispecific single-chain antibody construct which targets epithelial-cell-adhesion-molecule (EpCAM) on tumor cells and also contains a CD3 binding region, against primary uterine and ovarian CS cell lines.

methodsEpCAM expression was evaluated by flow cytometry in a total of 5 primary CS cell lines. Sensitivity to solitomab-dependent-cellular-cytotoxicity (ADCC) was tested against the panel of primary CS cell lines expressing different levels of EpCAM in standard 4 h (51)Cr release-assays. The proliferative activity, activation, cytokine secretion (i.e., Type I vs Type II) and cytotoxicity of solitomab in autologous tumor-associated-T cells (TAL) in the pleural fluid of a CS patient were also evaluated by CFSE and flow-cytometry assays.

resultsSurface expression of EpCAM was found in 80.0 % (4 out of 5) of the CS cell lines tested by flow cytometry. EpCAM positive cell lines were found resistant to NK or T-cell-mediated killing after exposure to peripheral blood lymphocytes (PBL) in 4-h chromium-release assays (mean killing ± SEM = 1.1 ± 1.6 %, range 0-5.3 % after incubation of EpCAM positive cell lines with control BiTE®). In contrast, after incubation with solitomab, EpCAM positive CS cells became highly sensitive to T-cell-cytotoxicity (mean killing ± SEM of 19.7 ± 6.3 %; range 10.0-32.0 %; P < 0.0001). Ex vivo incubation of autologous TAL with EpCAM expressing malignant cells in pleural effusion with solitomab, resulted in a significant increase in T-cell proliferation in both CD4+ and CD8+ T cells, increase in T-cell activation markers (i.e., CD25 and HLA-DR), and a reduction in number of viable CS cells in the exudate (P < 0.001).

conclusionsSolitomab may represent an effective treatment for patients with recurrent/metastatic and/or chemo-resistant CS overexpressing EpCAM.

Indexed as

AgedAntibodies, BispecificAntigens, NeoplasmAntineoplastic AgentsCarcinosarcomaCD3 ComplexCell Adhesion MoleculesCell Line, TumorCell ProliferationCoculture TechniquesCytokinesCytotoxicity, ImmunologicDrug Resistance, NeoplasmEpithelial Cell Adhesion MoleculeFemaleFlow CytometryAntibodies, BispecificAntigens, NeoplasmAntineoplastic AgentsCD3 ComplexCell Adhesion MoleculesCytokinesEPCAM protein, humanEpithelial Cell Adhesion MoleculeSolitomab

Identifiers

PMID26474755
PMCPMC4609066
OpenAlexW2147947369

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.