Evidence map›Paper›PMID 34413165›Full record

ArticleJournal for immunotherapy of cancer2021

Hypermethylation of CD19 promoter enables antigen-negative escape to CART-19 in vivo and in vitro.

Aneta Ledererova, Lenka Dostalova, Veronika Kozlova, Helena Peschelova, Adriana Ladungova, Martin Culen, Tomas Loja, Jan Verner, Sarka Pospisilova, Michal Smida and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 11% 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

31 citing papers in PubMed, 34 citations in OpenAlex.

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  13. FcRL1, a New B-Cell-Activating Co-Receptor.International journal of molecular sciences · 2025
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  18. Finding Your CAR: The Road Ahead for Engineered T Cells.The American journal of pathology · 2024
    Review
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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 1 institution in 1 country.

Aneta Ledererova *Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Lenka Dostalova *Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Veronika Kozlova *Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Helena PeschelovaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Adriana LadungovaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Martin CulenCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Tomas LojaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Jan VernerCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Sarka PospisilovaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Michal SmidaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic vero.mancikova@gmail.com michal.smida@ceitec.muni.cz.ORCID 0000-0002-7335-3435
Veronika MancikovaCentral European Institute of Technology, Masaryk University, Brno, Czech Republic vero.mancikova@gmail.com michal.smida@ceitec.muni.cz.ORCID 0000-0002-8155-9927
Central European Institute of Technology · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAnti-CD19 chimeric antigen receptor T cells (CART-19) frequently induce remissions in hemato-oncological patients with recurred and/or refractory B-cell tumors. However, malignant cells sometimes escape the immunotherapeutic targeting by

methodsHerein, we studied the mechanism of antigen loss in an in vivo CD19-negative recurrence model of chronic lymphocytic leukemia (CLL) to CART-19, established using NOD-

resultsIn our in vivo CLL recurrence model, up to 70% of CART-19-treated mice eventually recurred with CD19-negative disease weeks after initial positive response. We found that the lack of CD19 expression was caused by promoter DNA hypermethylation. Importantly, the expression loss was partially reversible by treatment with a demethylating agent. Moreover, this escape mechanism was common for 3 B-cell immortalized lines as well as primary CLL cells, as assessed by in vitro coculture experiments.

conclusionsEpigenetically driven antigen escape could represent a novel, yet at least partially reversible, means of CD19 loss to CART-19 in B-cell tumors.

Indexed as

AnimalsAntigens, CD19DNA MethylationFemaleHumansMaleMiceReceptors, Antigen, T-CellAntigens, CD19CTL019 chimeric antigen receptorReceptors, Antigen, T-CellantigensB-lymphocyteschimeric antigenhematologic neoplasmsreceptorstranslational medical research

Identifiers

PMID34413165
PMCPMC8378389
OpenAlexW3195728868

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.