Evidence map›Paper›PMID 29422056›Full record

ArticleJournal of translational medicine2018

Turning the tables on cytomegalovirus: targeting viral Fc receptors by CARs containing mutated CH2-CH3 IgG spacer domains.

Julia Proff, Charlotte U Brey, Armin Ensser, Wolfgang Holter, Manfred Lehner

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
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  6. Synergistic integration of mRNA-LNP with CAR-engineered immune cells: Pioneering progress in immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
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  17. The role of NK cells in fighting the virus infection and sepsis.International journal of medical sciences · 2021
    Review
  18. Article
  19. Dendritic cell biology and its role in tumor immunotherapy.Journal of hematology & oncology · 2020
    Review
  20. Advances in Fungal Peptide Vaccines.Journal of fungi (Basel, Switzerland) · 2020
    Review
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

5 authors at 4 institutions in 4 countries.

Julia ProffChildren's Cancer Research Institute, Zimmermannplatz 10, 1090, Vienna, Austria.
Charlotte U BreyChildren's Cancer Research Institute, Zimmermannplatz 10, 1090, Vienna, Austria.
Armin EnsserInstitute for Clinical and Molecular Virology, Universitätsklinikum Erlangen, Schlossgarten 4, 91054, Erlangen, Germany.
Wolfgang HolterChildren's Cancer Research Institute, Zimmermannplatz 10, 1090, Vienna, Austria.
Manfred LehnerChildren's Cancer Research Institute, Zimmermannplatz 10, 1090, Vienna, Austria. manfred.lehner@ccri.at.ORCID 0000-0002-5776-4218
Ludwig Boltzmann Institute for Cancer Research · ATCancer Research Institute of the Slovak Academy of Sciences · SKSt Anna Children's Hospital · ATUniversitätsklinikum Erlangen · DE

Funding

Austrian Science Fund FWF W 1224Deutsche Forschungsgemeinschaft CRC 796Deutsche Forschungsgemeinschaft TP B1Interdisciplinary Center for Clinical Research Erlangen A66Wilhelm Sander Foundation 2013.105.1
6 · The paper itself

Abstract

backgroundDuring infection with human cytomegalovirus (HCMV) several viral proteins occur on cell surfaces in high quantity. We thus pursue an HLA-independent approach for immunotherapy of HCMV using chimeric antigen receptors (CARs) and bispecific BiTE

methodsReplication of GFP-encoding recombinant HCMV in fibroblasts in the presence and absence of supernatants from T cell co-cultures plus/minus cytokine neutralizing antibodies was analyzed by flow cytometry. CARs with wild type and mutated CH2-CH3 domains were expressed in human T cells by mRNA electroporation, and the function of the CARs was assessed by quantifying T cell cytokine secretion.

resultsWe confirm and extend previous evidence of antiviral cytokine effects and demonstrate that CAR T cells strongly block HCMV replication in fibroblasts mainly by combined secretion of IFN-γ and TNF. Furthermore, we show that fibroblasts infected with HCMV strains AD169 and Towne starting from day 3 have a high capacity for binding of human IgG1 and also strongly activate T cells expressing a CAR with CH2-CH3 domain. Importantly, we further show that mutations in the CH2-CH3 domain of IgG1 and IgG4, which were previously reported to rescue CAR T cell function by abrogating interaction with endogenous Fc receptors (FcRs), still enable recognition of FcRs encoded by HCMV.

conclusionsOur findings identify HCMV-encoded FcRs as an attractive additional target for HCMV immunotherapy by CARs and possibly bispecific antibodies. The use of specifically mutated IgG domains that bind to HCMV-FcRs without recognizing endogenous FcRs may supersede screening for novel binders directed against individual HCMV-FcRs.

Indexed as

Cell DeathCytomegalovirusFibroblastsHumansImmunoglobulin GInterferon-gammaMaleMutationProtein DomainsReceptors, Chimeric AntigenReceptors, FcT-LymphocytesTumor Necrosis Factor-alphaViral Envelope ProteinsVirus Replicationglycoprotein B, SimplexvirusImmunoglobulin GInterferon-gammaReceptors, Chimeric AntigenReceptors, FcTumor Necrosis Factor-alphaViral Envelope ProteinsCH2–CH3 domainChimeric antigen receptor (CAR)CytomegalovirusFc receptorsGlycoprotein B (gB)IgGInterferon gamma (IFN-γ)Tumor necrosis factor (TNF)

Identifiers

PMID29422056
PMCPMC5804023
OpenAlexW2793306083

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.