Evidence map›Paper›PMID 31500597›Full record

ArticleBMC cancer2019

CD171- and GD2-specific CAR-T cells potently target retinoblastoma cells in preclinical in vitro testing.

Lena Andersch, Josefine Radke, Anika Klaus, Silke Schwiebert, Annika Winkler, Elisa Schumann, Laura Grunewald, Felix Zirngibl, Carina Flemmig, Michael C Jensen and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  5. Retinoblastoma and Its Tumor Microenvironment.Current oncology (Toronto, Ont.) · 2026
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  12. Targeting GPC2 on Intraocular and CNS Metastatic Retinoblastomas with Local and Systemic Delivery of CAR T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
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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

16 authors at 7 institutions in 2 countries.

Lena AnderschDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Josefine RadkeDepartment of Neuropathology, Charitéplatz 1, Charité, Universitätsmedizin Berlin, 10117, Berlin, Germany.
Anika KlausDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Silke SchwiebertDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Annika WinklerDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Elisa SchumannDepartment of Neuropathology, Charitéplatz 1, Charité, Universitätsmedizin Berlin, 10117, Berlin, Germany.
Laura GrunewaldDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Felix ZirngiblDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Carina FlemmigDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Michael C JensenBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Claudia RossigDepartment of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.
Antonia JoussenDepartment of Ophthalmology, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
Anton HenssenDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Angelika EggertDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Johannes H SchulteDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
Annette KünkeleDepartment of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. Annette.Kuenkele@charite.de.ORCID http://orcid.org/0000-0002-8406-5412
Humboldt-Universität zu Berlin · DEGerman Cancer Research Center · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DECharité - Universitätsmedizin Berlin · DEDeutschen Konsortium für Translationale Krebsforschung · DESeattle Children's Hospital · USUniversity Hospital Münster · DE

Funding

Berlin Institute of Health Clinical Scientist Program
6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR)-based T cell therapy is in early clinical trials to target the neuroectodermal tumor, neuroblastoma. No preclinical or clinical efficacy data are available for retinoblastoma to date. Whereas unilateral intraocular retinoblastoma is cured by enucleation of the eye, infiltration of the optic nerve indicates potential diffuse scattering and tumor spread leading to a major therapeutic challenge. CAR-T cell therapy could improve the currently limited therapeutic strategies for metastasized retinoblastoma by simultaneously killing both primary tumor and metastasizing malignant cells and by reducing chemotherapy-related late effects.

methodsCD171 and GD2 expression was flow cytometrically analyzed in 11 retinoblastoma cell lines. CD171 expression and T cell infiltration (CD3

resultsAll retinoblastoma cell lines investigated expressed CD171 and GD2. CD171 was expressed in 15/30 primary retinoblastomas. Retinoblastoma cell encounter strongly activated both CD171-specific and GD2-specific CAR-T cells. Targeting either CD171 or GD2 effectively killed all retinoblastoma cell lines examined. Similar activation and killing ability for either target was achieved by all CAR constructs irrespective of the length of the extracellular spacers and the co-stimulatory domain. Cell lines differentially lost tumor antigen expression upon CAR-T cell encounter, with CD171 being completely lost by all tested cell lines and GD2 further down-regulated in cell lines expressing low GD2 levels before CAR-T cell challenge. Alternating the CAR-T cell target in sequential challenges enhanced retinoblastoma cell killing.

conclusionBoth CD171 and GD2 are effective targets on human retinoblastoma cell lines, and CAR-T cell therapy is highly effective against retinoblastoma in vitro. Targeting of two different antigens by sequential CAR-T cell applications enhanced tumor cell killing and preempted tumor antigen loss in preclinical testing.

Indexed as

Cell- and Tissue-Based TherapyReceptors, Chimeric AntigenCell Line, TumorChildChild, PreschoolCytotoxicity, ImmunologicFemaleGangliosidesHumansInfantMaleNeural Cell Adhesion Molecule L1RetinoblastomaRetrospective StudiesT-Lymphocytesganglioside, GD2GangliosidesNeural Cell Adhesion Molecule L1Receptors, Chimeric AntigenAdoptive T-cell immunotherapyAntigen lossCD171GD2RetinoblastomaSequential CAR-T cell therapy

Identifiers

PMID31500597
PMCPMC6732842
OpenAlexW2972979709

What OpenQuestion holds

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LicenceCC BY
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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.