Evidence map›Paper›PMID 40324075›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Quadruple adenine base-edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease-engineered T cells.

Nils W Engel, Israel Steinfeld, Daniel Ryan, Kusala Anupindi, Samuel Kim, Nils Wellhausen, Linhui Chen, Katherine Wilkins, Daniel J Baker, Philipp C Rommel and 8 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

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  11. Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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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

18 authors.

Nils W EngelCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Israel SteinfeldAgilent Research Laboratories, Santa Clara, CA 95051.
Daniel RyanAgilent Research Laboratories, Santa Clara, CA 95051.
Kusala AnupindiCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Samuel KimCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Nils WellhausenCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Linhui ChenInstitute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Katherine WilkinsAgilent Research Laboratories, Santa Clara, CA 95051.
Daniel J BakerCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-6400-7426
Philipp C RommelCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-9790-4086
Danuta JarochaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Mercy GohilCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Qian ZhangCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Michael C MiloneCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Joseph A FraiettaCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Megan DavisCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Regina M YoungCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Carl H JuneCenter for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0003-0241-3557

Funding

Project 3U54CA244711 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2019 to 2022
$7.1M
Agilent Foundation (Agilent Technologies Foundation) Thought Leader Award 2020Gilead | Kite Pharma Sponsored ResearchNCI NIH HHS U54 CA244711US NIH, National Cancer Institute 1-U54 CA244711
6 · The paper itself

Abstract

Genome-editing technologies have enabled the clinical development of allogeneic cellular therapies, yet the optimal gene-editing modality for multiplex editing of therapeutic T cell product manufacturing remains elusive. In this study, we conducted a comprehensive comparison of CRISPR/Cas9 nuclease and adenine base editor (ABE) technologies in generating allogeneic chimeric antigen receptor (CAR) T cells, utilizing extensive in vitro and in vivo analyses. Both methods achieved high editing efficiencies across four target genes, critical for mitigating graft-versus-host disease and allograft rejection:

Indexed as

AdenineCRISPR-Cas SystemsGene EditingReceptors, Chimeric AntigenT-LymphocytesAnimalsGraft vs Host DiseaseHumansImmunotherapy, AdoptiveMiceAdenineReceptors, Chimeric Antigenadenine base editorchimeric antigen receptorCRISPR/Cas9

Identifiers

PMID40324075
PMCPMC12107175

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.