Evidence map›Paper›PMID 31415244›Full record

ArticleJCI insight2019

ROR1-CAR T cells are effective against lung and breast cancer in advanced microphysiologic 3D tumor models.

Lars Wallstabe, Claudia Göttlich, Lena C Nelke, Johanna Kühnemundt, Thomas Schwarz, Thomas Nerreter, Hermann Einsele, Heike Walles, Gudrun Dandekar, Sarah L Nietzer and 1 more

Abstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

122 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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62 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

11 authors.

Lars WallstabeMedizinische Klinik und Poliklinik II and.
Claudia GöttlichTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Lena C NelkeTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Johanna KühnemundtTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Thomas SchwarzTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Thomas NerreterMedizinische Klinik und Poliklinik II and.
Hermann EinseleMedizinische Klinik und Poliklinik II and.
Heike WallesTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Gudrun DandekarTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Sarah L NietzerTissue Engineering and Regenerative Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Michael HudecekMedizinische Klinik und Poliklinik II and.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Solid tumors impose immunologic and physical barriers to the efficacy of chimeric antigen receptor (CAR) T cell therapy that are not reflected in conventional preclinical testing against singularized tumor cells in 2-dimensional culture. Here, we established microphysiologic three-dimensional (3D) lung and breast cancer models that resemble architectural and phenotypical features of primary tumors and evaluated the antitumor function of receptor tyrosine kinase-like orphan receptor 1-specific (ROR1-specific) CAR T cells. 3D tumors were established from A549 (non-small cell lung cancer) and MDA-MB-231 (triple-negative breast cancer) cell lines on a biological scaffold with intact basement membrane (BM) under static and dynamic culture conditions, which resulted in progressively increasing cell mass and invasive growth phenotype (dynamic > static; MDA-MB-231 > A549). Treatment with ROR1-CAR T cells conferred potent antitumor effects. In dynamic culture, CAR T cells actively entered arterial medium flow and adhered to and infiltrated the tumor mass. ROR1-CAR T cells penetrated deep into tumor tissue and eliminated multiple layers of tumor cells located above and below the BM. The microphysiologic 3D tumor models developed in this study are standardized, scalable test systems that can be used either in conjunction with or in lieu of animal testing to interrogate the antitumor function of CAR T cells and to obtain proof of concept for their safety and efficacy before clinical application.

Indexed as

Animal Testing AlternativesCell Culture TechniquesCell Line, TumorFemaleHumansImmunotherapy, AdoptiveLung NeoplasmsReceptors, Chimeric AntigenReceptor Tyrosine Kinase-like Orphan ReceptorsSingle-Chain AntibodiesSpheroids, CellularT-LymphocytesTriple Negative Breast NeoplasmsReceptors, Chimeric AntigenReceptor Tyrosine Kinase-like Orphan ReceptorsROR1 protein, humanSingle-Chain AntibodiesBreast cancerImmunologyImmunotherapyLung cancerOncology

Identifiers

PMID31415244
PMCPMC6795380

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.