Evidence map›Paper›PMID 34035409›Full record

ArticleLeukemia2021

Base-edited CAR T cells for combinational therapy against T cell malignancies.

Christos Georgiadis, Jane Rasaiyaah, Soragia Athina Gkazi, Roland Preece, Aniekan Etuk, Abraham Christi, Waseem Qasim

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
8.3field-weighted citation impact, top 1% 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

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.

  1. Pooled it
  2. Article
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  4. Review
  5. Gene therapy: The current trajectory of clinical and commercial translation.Progress in biophysics and molecular biology · 2026
    Review
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32 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

7 authors at 1 institution in 1 country.

Christos Georgiadis *Molecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK.ORCID http://orcid.org/0000-0003-0031-8396
Jane Rasaiyaah *Molecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK.
Soragia Athina GkaziMolecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK.
Roland PreeceMolecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK.
Aniekan EtukMolecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK.
Abraham ChristiMolecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK.
Waseem QasimMolecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, WC1N 1EH, London, UK. W.Qasim@UCL.ac.uk.ORCID http://orcid.org/0000-0001-8353-4494
Great Ormond Street Hospital · GB

Funding

Department of HealthWellcome Trust
6 · The paper itself

Abstract

Targeting T cell malignancies using chimeric antigen receptor (CAR) T cells is hindered by 'T v T' fratricide against shared antigens such as CD3 and CD7. Base editing offers the possibility of seamless disruption of gene expression of problematic antigens through creation of stop codons or elimination of splice sites. We describe the generation of fratricide-resistant T cells by orderly removal of TCR/CD3 and CD7 ahead of lentiviral-mediated expression of CARs specific for CD3 or CD7. Molecular interrogation of base-edited cells confirmed elimination of chromosomal translocations detected in conventional Cas9 treated cells. Interestingly, 3CAR/7CAR co-culture resulted in 'self-enrichment' yielding populations 99.6% TCR-/CD3-/CD7-. 3CAR or 7CAR cells were able to exert specific cytotoxicity against leukaemia lines with defined CD3 and/or CD7 expression as well as primary T-ALL cells. Co-cultured 3CAR/7CAR cells exhibited highest cytotoxicity against CD3 + CD7 + T-ALL targets in vitro and an in vivo human:murine chimeric model. While APOBEC editors can reportedly exhibit guide-independent deamination of both DNA and RNA, we found no problematic 'off-target' activity or promiscuous base conversion affecting CAR antigen-specific binding regions, which may otherwise redirect T cell specificity. Combinational infusion of fratricide-resistant anti-T CAR T cells may enable enhanced molecular remission ahead of allo-HSCT for T cell malignancies.

Indexed as

AnimalsAntigens, CD7CD3 ComplexCell Line, TumorCRISPR-Cas SystemsFemaleGene EditingHumansImmunotherapy, AdoptiveLeukemia, T-CellMiceMice, Inbred NODMice, SCIDT-LymphocytesXenograft Model Antitumor AssaysAntigens, CD7CD3 Complex

Identifiers

PMID34035409
PMCPMC8632682
OpenAlexW3164622970

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.