Evidence map›Paper›PMID 20851867›Full record

ArticleHaematologica2010

HuMab-7D8, a monoclonal antibody directed against the membrane-proximal small loop epitope of CD20 can effectively eliminate CD20 low expressing tumor cells that resist rituximab-mediated lysis.

Tom van Meerten, Henk Rozemuller, Samantha Hol, Petra Moerer, Mieke Zwart, Anton Hagenbeek, Wendy J M Mackus, Paul W H I Parren, Jan G J van de Winkel, Saskia B Ebeling and 1 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 32 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

11 authors at 2 institutions in 1 country.

Tom van MeertenDepartment of Immunology, Medical Center Utrecht, Utrecht, the Netherlands. tmeerten@umcutrecht.nl
Henk Rozemuller
Samantha Hol
Petra Moerer
Mieke Zwart
Anton Hagenbeek
Wendy J M Mackus
Paul W H I Parren
Jan G J van de Winkel
Saskia B Ebeling
Anton C Martens
University Medical Center Utrecht · NLGenmab (Netherlands) · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIncorporation of the chimeric CD20 monoclonal antibody rituximab in the treatment schedule of patients with non-Hodgkin's lymphoma has significantly improved outcome. Despite this success, about half of the patients do not respond to treatment or suffer from a relapse and additional therapy is required. A low CD20-expression level may in part be responsible for resistance against rituximab. We therefore investigated whether the CD20-expression level related resistance to rituximab could be overcome by a new group of CD20 mAbs (HuMab-7D8 and ofatumumab) targeting a unique membrane-proximal epitope on the CD20 molecule. DESIGN AND

methodsBy retroviral transduction of the CD20 gene into CD20-negative cells and clonal selection of transduced cells a system was developed in which the CD20-expression level is the only variable. These CD20 transduced cells were used to study the impact of rituximab and HuMab-7D8 mediated complement-dependent cytotoxicity. To study the in vivo efficacy of these mAbs an in vivo imaging system was generated by retroviral expression of the luciferase gene in the CD20-positive cells.

resultsWe show that HuMab-7D8 efficiently killed CD20(low) cells that are not susceptible to rituximab-induced killing in vitro. In a mouse xenograft model, we observed a comparable increase in survival time between HuMab-7D8 and rituximab-treated mice. Most significantly, however, HuMab-7D8 eradicated all CD20-expressing cells both in the periphery as well as in the bone marrow whereas after rituximab treatment CD20(low) cells survived.

conclusionsCells that are insensitive to in vitro and in vivo killing by rituximab as the result of their low CD20-expression profile may be efficiently killed by an antibody against the membrane-proximal epitope on CD20. Such antibodies should, therefore, be explored to overcome rituximab resistance in the clinic.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, Murine-DerivedAntigens, CD20Cell Line, TumorCytotoxicity, ImmunologicEpitopesFlow CytometryGreen Fluorescent ProteinsHumansLeukemia, ExperimentalLuciferasesLuminescent MeasurementsMembrane MicrodomainsMiceProtein TransportAntibodies, MonoclonalAntibodies, Monoclonal, Murine-DerivedAntigens, CD20EpitopesGreen Fluorescent ProteinsLuciferasesRituximab

Identifiers

PMID20851867
PMCPMC2995564
OpenAlexW2160690356

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.