Evidence map›Paper›PMID 31981978›Full record

ArticleEBioMedicine2020

DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing.

Patrick J Engelberts, Ida H Hiemstra, Bart de Jong, Danita H Schuurhuis, Joyce Meesters, Irati Beltran Hernandez, Simone C Oostindie, Joost Neijssen, Edward N van den Brink, G Jean Horbach and 6 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 2 pooled it
6.7field-weighted citation impact, top 2% 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

111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 163 citations in OpenAlex.

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  5. Molecular Profiling of Tisotumab Vedotin-Treated Patients Identifies Immune Pathways Associated with Clinical Activity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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51 more citing papers are in PubMed but not listed here.

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

16 authors at 2 institutions in 1 country.

Patrick J EngelbertsGenmab, Utrecht, The Netherlands.
Ida H HiemstraGenmab, Utrecht, The Netherlands.
Bart de JongGenmab, Utrecht, The Netherlands.
Danita H SchuurhuisGenmab, Utrecht, The Netherlands.
Joyce MeestersGenmab, Utrecht, The Netherlands.
Irati Beltran HernandezGenmab, Utrecht, The Netherlands.
Simone C OostindieGenmab, Utrecht, The Netherlands; Dept of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Joost NeijssenGenmab, Utrecht, The Netherlands.
Edward N van den BrinkGenmab, Utrecht, The Netherlands.
G Jean HorbachGenmab, Utrecht, The Netherlands.
Sandra VerploegenGenmab, Utrecht, The Netherlands.
Aran F LabrijnGenmab, Utrecht, The Netherlands.
Theodora SalcedoGenmab, Utrecht, The Netherlands.
Janine SchuurmanGenmab, Utrecht, The Netherlands.
Paul W H I ParrenGenmab, Utrecht, The Netherlands; Dept of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Esther C W BreijGenmab, Utrecht, The Netherlands. Electronic address: EBJ@genmab.com.
Genmab (Netherlands) · NLLeiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDuoBody®-CD3xCD20 (GEN3013) is a full-length human IgG1 bispecific antibody (bsAb) recognizing CD3 and CD20, generated by controlled Fab-arm exchange. Its Fc domain was silenced by introduction of mutations L234F L235E D265A.

methodsT-cell activation and T-cell-mediated cytotoxicity were measured by flow cytometry following co-culture with tumour cells. Anti-tumour activity of DuoBody-CD3xCD20 was assessed in humanized mouse models in vivo. Non-clinical safety studies were performed in cynomolgus monkeys.

findingsDuoBody-CD3xCD20 induced highly potent T-cell activation and T-cell-mediated cytotoxicity towards malignant B cells in vitro. Comparison of DuoBody-CD3xCD20 to CD3 bsAb targeting alternative B-cell antigens, or to CD3xCD20 bsAb generated using alternative CD20 Ab, emphasized its exceptional potency. In vitro comparison with other CD3xCD20 bsAb in clinical development showed that DuoBody-CD3xCD20 was significantly more potent than three other bsAb with single CD3 and CD20 binding regions and equally potent as a bsAb with a single CD3 and two CD20 binding regions. DuoBody-CD3xCD20 showed promising anti-tumour activity in vivo, also in the presence of excess levels of a CD20 Ab that competes for binding. In cynomolgus monkeys, DuoBody-CD3xCD20 demonstrated profound and long-lasting B-cell depletion from peripheral blood and lymphoid organs, which was comparable after subcutaneous and intravenous administration. Peak plasma levels of DuoBody-CD3xCD20 were lower and delayed after subcutaneous administration, which was associated with a reduction in plasma cytokine levels compared to intravenous administration, while bioavailability was comparable.

interpretationBased on these preclinical studies, a clinical trial was initiated to assess the clinical safety of subcutaneous DuoBody-CD3xCD20 in patients with B-cell malignancies.

fundingGenmab.

Indexed as

Cytotoxicity, ImmunologicAnimalsAntibodies, BispecificAntibody-Dependent Cell CytotoxicityAntibody SpecificityAntigens, CD20Antineoplastic Agents, ImmunologicalCD3 ComplexCell Line, TumorDisease Models, AnimalDose-Response Relationship, DrugFemaleHumansLeukemia, B-CellLymphocyte ActivationLymphoma, B-CellAntibodies, BispecificAntigens, CD20Antineoplastic Agents, ImmunologicalCD3 ComplexRecombinant ProteinsB cell malignancyBispecific antibodyCD20CD3Subcutaneous administrationT cell redirection

Identifiers

PMID31981978
PMCPMC6992935
OpenAlexW3001767756

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.