Evidence map›Paper›PMID 33173582›Full record

ArticleClinical & translational immunology2020

Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy-induced cytokine release syndrome.

Alba Matas-Céspedes, Lee Brown, Krishnaa T Mahbubani, Bethany Bareham, Jackie Higgins, Michelle Curran, Lolke de Haan, Jean-Martin Lapointe, Richard Stebbings, Kourosh Saeb-Parsy

Open access · goldAbstract read
In one paragraph

Article in Clinical & translational immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 28% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. 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

10 authors at 2 institutions in 4 countries.

Alba Matas-CéspedesClinical Pharmacology and Safety Sciences R&D AstraZeneca Cambridge UK.ORCID https://orcid.org/0000-0003-2121-2793
Lee BrownClinical Pharmacology and Safety Sciences R&D AstraZeneca Cambridge UK.
Krishnaa T MahbubaniDepartment of Surgery University of Cambridge and NIHR Cambridge Biomedical Campus Cambridge UK.
Bethany BarehamDepartment of Surgery University of Cambridge and NIHR Cambridge Biomedical Campus Cambridge UK.ORCID https://orcid.org/0000-0003-1892-8256
Jackie HigginsDepartment of Surgery University of Cambridge and NIHR Cambridge Biomedical Campus Cambridge UK.
Michelle CurranClinical Pharmacology and Safety Sciences R&D AstraZeneca Cambridge UK.
Lolke de HaanClinical Pharmacology and Safety Sciences R&D AstraZeneca Cambridge UK.
Jean-Martin LapointeClinical Pharmacology and Safety Sciences R&D AstraZeneca Cambridge UK.
Richard StebbingsClinical Pharmacology and Safety Sciences R&D AstraZeneca Cambridge UK.
Kourosh Saeb-ParsyDepartment of Surgery University of Cambridge and NIHR Cambridge Biomedical Campus Cambridge UK.ORCID https://orcid.org/0000-0002-0633-3696
AstraZeneca (United Kingdom) · GBUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesHumanised mice have emerged as valuable models for pre-clinical testing of the safety and efficacy of immunotherapies. Given the variety of models available, selection of the most appropriate humanised mouse model is critical in study design. Here, we aimed to develop a model for predicting cytokine release syndrome (CRS) while minimising graft-

methodsTo overcome donor-induced variation, we directly compared the

resultsPBMC- and SPMC-reconstituted NSG mice showed short-term survival, with engrafted human T cells exhibiting mostly an effector memory phenotype. Survival in SPMC-reconstituted NSG-dKO mice was significantly longer. Conversely, both BM and UCB-HSC models showed longer survival, without demonstrable GvHD and a more naïve T-cell phenotype. PBMC- and SPMC-reconstituted mice, but not BM-HSC or UCB-HSC mice, experienced severe clinical signs of CRS upon administration of OKT3.

conclusionPBMC- and SPMC-reconstituted NSG mice better predict OKT3-mediated CRS. The SPMC model allows generation of large experimental groups, and the use of NSG-dKO mice mitigates the limitation of early GvHD.

Indexed as

animal modelscytokine release syndromehumanized miceimmune systemimmunotherapypre‐clinical safety assessment

Identifiers

PMID33173582
PMCPMC7641894
OpenAlexW3095786575

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.