Evidence map›Paper›PMID 26515978›Full record

ArticleCancer immunology, immunotherapy : CII2015

Stability and activity of MCSP-specific chimeric antigen receptors (CARs) depend on the scFv antigen-binding domain and the protein backbone.

Christian Krug, Katrin Birkholz, Alexander Paulus, Michael Schwenkert, Patrick Schmidt, Nicole Hoffmann, Andreas Hombach, Georg Fey, Hinrich Abken, Gerold Schuler and 3 more

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

37 citing papers in PubMed, 51 citations in OpenAlex.

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  12. CAR-T Cell Therapy: From the Shop to Cancer Therapy.International journal of molecular sciences · 2023
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  14. RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023
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  16. mRNA: A promising platform for cancer immunotherapy.Advanced drug delivery reviews · 2023
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  17. 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

13 authors at 3 institutions in 1 country.

Christian KrugDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany.
Katrin BirkholzDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany.
Alexander PaulusDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany.
Michael SchwenkertDepartment of Biology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.
Patrick SchmidtCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Nicole HoffmannCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Andreas HombachCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Georg FeyDepartment of Biology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.
Hinrich AbkenCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Gerold SchulerDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany.
Beatrice Schuler-ThurnerDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany.
Jan DörrieDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany.
Niels SchaftDepartment of Dermatology, Universitätsklinikum Erlangen, Hartmannstraße 14, 91052, Erlangen, Germany. niels.schaft@uk-erlangen.de.
Universitätsklinikum Erlangen · DEUniversity of Cologne · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-modified T cells emerged as effective tools in the immunotherapy of cancer but can produce severe on-target off-tissue toxicities. This risk can conceivably be overcome, at least partially, by transient transfection. The design of CARs, however, has so far not been optimized for use in non-permanent T cell modification. Here we compared the performance of T cells modified with three different first- and second-generation CARs, each specific for MCSP (HMW-MAA) which is commonly expressed by melanoma cells. Upon RNA transfer, the expression of all receptors was limited in time. The second-generation CARs, which combined CD28-CD3ζ signaling, were expressed at higher levels and more prolonged than first-generation CARs with CD3ζ only. The CD28 domain increased the cytokine production, but had only an indirect effect on the lytic capacity, by prolonging the CAR expression. Especially for the second-generation CARs, the scFv clearly impacted the level and duration of CAR expression and the T cell performance. Thus, we identified a CAR high in both expression and anti-tumor cell reactivity. T cells transfected with this CAR increased the mean survival time of mice after challenge with melanoma cells. To facilitate clinical application, this CAR was used to redirect T cells from late-stage melanoma patients by RNA transfection. These T cells mediated effective antigen-specific tumor cell lysis and release of pro-inflammatory cytokines, even after cryoconservation of the transfected T cells. Taken together, the analysis identified a CAR with superior anti-melanoma performance after RNA transfer which is a promising candidate for clinical exploration.

Indexed as

AnimalsCarrier ProteinsCell Line, TumorDisease Models, AnimalGene Expression Regulation, NeoplasticHumansMelanomaMiceMitochondrial ProteinsProtein StabilityProtein Structure, TertiaryReceptors, Antigen, T-CellSingle-Chain AntibodiesCarrier ProteinsMitochondrial ProteinsReceptors, Antigen, T-CellSingle-Chain AntibodiesSMCP protein, humanAdoptive T cell therapyChimeric antigen receptorMelanomaMelanoma-associated chondroitin sulfate proteoglycan (MCSP)mRNA transfectionSingle-chain variable fragment (scFv)

Identifiers

PMID26515978
PMCPMC11028909
OpenAlexW1904657502

What OpenQuestion holds

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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.