Evidence map›Paper›PMID 25652098›Full record

ArticleGene therapy2015

Inclusion of an IgG1-Fc spacer abrogates efficacy of CD19 CAR T cells in a xenograft mouse model.

H Almåsbak, E Walseng, A Kristian, M R Myhre, E M Suso, L A Munthe, J T Andersen, M Y Wang, G Kvalheim, G Gaudernack and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
–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

75 citing papers in PubMed.

  1. Review
  2. Depletion of CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023
    Review
  17. Review
  18. Review
  19. Review
  20. Article

15 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.

H AlmåsbakSection for Cell Therapy, Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
E Walseng1] Department of Immunology, Oslo University Hospital Radiumhospitalet, Oslo, Norway [2] Department of Cancer Biology, Scripps Research Institute, Jupiter, FL, USA.
A Kristian1] Department of Tumor Biology, Oslo University Hospital Radiumhospitalet, Oslo, Norway [2] KG Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
M R MyhreSection for Cell Therapy, Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
E M SusoSection for Cell Therapy, Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
L A Munthe1] Centre for Immune Regulation and Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway [2] Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
J T AndersenCentre for Immune Regulation and Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
M Y WangSection for Cell Therapy, Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
G KvalheimSection for Cell Therapy, Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
G GaudernackDepartment of Immunology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
J A KyteSection for Cell Therapy, Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer therapy with T cells expressing chimeric antigen receptors (CARs) has produced remarkable clinical responses in recent trials, but also severe side effects. Whereas most protocols use permanently reprogrammed T cells, we have developed a platform for transient CAR expression by mRNA electroporation. This approach may be useful for safe clinical testing of novel receptors, or when a temporary treatment period is desirable. Herein, we investigated therapy with transiently redirected T cells in vitro and in a xenograft mouse model. We constructed a series of CD19-specific CARs with different spacers and co-stimulatory domains (CD28, OX40 or CD28-OX40). The CAR constructs all conferred T cells with potent CD19-specific activity in vitro. Unexpectedly, the constructs incorporating a commonly used IgG1-CH2CH3 spacer showed lack of anti-leukemia activity in vivo and induced severe, partly CD19-independent toxicity. By contrast, identical CAR constructs without the CH2-domain eradicated leukemia in vivo, without notable toxicity. Follow-up studies demonstrated that the CH2CH3-spacer bound soluble mouse Fcγ-receptor I and mediated off-target T-cell activation towards murine macrophages. Our findings highlight the importance of non-signalling CAR elements and of in vivo studies. Finally, the results show that transiently redirected T cells control leukemia in mice and support the rationale for developing an mRNA-CAR platform.

Indexed as

AnimalsAntigens, CD19CD28 AntigensCell Line, TumorCells, CulturedGenetic TherapyHEK293 CellsHumansImmunotherapy, AdoptiveLeukemiaMacrophage ActivationMacrophagesMiceMice, Inbred NODReceptors, Antigen, T-CellReceptors, IgGAntigens, CD19CD28 AntigensReceptors, Antigen, T-CellReceptors, IgGReceptors, OX40Recombinant Proteins

Identifiers

PMID25652098

What OpenQuestion holds

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Read underepoch 390

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.