Evidence map›Paper›PMID 28441264›Full record

ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2017

CD19 Isoforms Enabling Resistance to CART-19 Immunotherapy Are Expressed in B-ALL Patients at Initial Diagnosis.

Jeannette Fischer, Claudia Paret, Khalifa El Malki, Francesca Alt, Arthur Wingerter, Marie A Neu, Bettina Kron, Alexandra Russo, Nadine Lehmann, Lea Roth and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

153 citing papers in PubMed, 241 citations in OpenAlex.

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  3. The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026
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93 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

15 authors at 2 institutions in 1 country.

Jeannette Fischer*Section of Pediatric Oncology, Children's Hospital, University Medical Center of the Johannes Gutenberg University, Mainz, Germany ‡Third Department of Medicine, University Medical Center of the Johannes Gutenberg University §Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University †University Cancer Center of the Johannes Gutenberg University, Mainz, Germany.
Claudia Paret
Khalifa El Malki
Francesca Alt
Arthur Wingerter
Marie A Neu
Bettina Kron
Alexandra Russo
Nadine Lehmann
Lea Roth
Eva-M Fehr
Sebastian Attig
Alexander Hohberger
Thomas Kindler
Jörg Faber
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy. In this work, we analyzed the expression of CD19 isoforms in a cohort of 14 children with CD19 B-ALL and 6 nonleukemia donors. We showed that an alternatively spliced CD19 mRNA isoform lacking exon 2, and therefore the CART-19 epitope, but not isoforms lacking the transmembrane and cytosolic domains are expressed in leukemic blasts at diagnosis in children and in the bone marrow of nonleukemia donors. Furthermore, we clarified the sequence of a further isoform lacking the epitope recognized by CART-19 therapy and disclosed the presence of new isoforms. In comparison with the children, we showed that alternatively spliced CD19 mRNA isoforms affecting exon 2 are also expressed in 6 adult patients with CD19 B-ALL. On top of that, one of the adults expressed an isoform lacking the CD19 transmembrane and cytosolic domains. In conclusion, we proved that some of the CD19 isoforms contributing to CART-19 escape already preexist at diagnosis and could evolve as a dominant clone during CART-19 therapy suggesting the application of combined treatment approaches.

Indexed as

AdolescentAdultAgedAged, 80 and overAntigens, CD19Cancer VaccinesChildChild, PreschoolCohort StudiesEpitopes, T-LymphocyteFemaleHumansImmunotherapy, AdoptiveInfantInfant, NewbornMaleAntigens, CD19Cancer VaccinesCD19 molecule, humanEpitopes, T-LymphocyteProtein IsoformsReceptors, Antigen, T-CellRecombinant Fusion Proteins

Identifiers

PMID28441264
PMCPMC5424577
OpenAlexW2609835530

What OpenQuestion holds

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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.