Evidence map›Paper›PMID 40341025›Full record

ArticleJournal for immunotherapy of cancer2025

Precision enhancement of CAR-NK cells through non-viral engineering and highly multiplexed base editing.

Minjing Wang, Joshua B Krueger, Alexandria K Gilkey, Erin M Stelljes, Mitchell G Kluesner, Emily J Pomeroy, Joseph G Skeate, Nicholas J Slipek, Walker S Lahr, Patricia N Claudio Vázquez and 8 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

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  19. Installation of dominant-negative mutations inMolecular therapy. Oncology · 2025
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Minjing WangDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0003-4725-8351
Joshua B KruegerDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0009-0002-7658-149X
Alexandria K GilkeyDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Erin M StelljesDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Mitchell G KluesnerDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Emily J PomeroyDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Joseph G SkeateDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0002-1765-5949
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Walker S LahrDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Patricia N Claudio VázquezDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Yueting ZhaoDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Jason B BellDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0003-4869-6476
Kendell ClementDepartment of Biomedical Informatics, The University of Utah, Salt Lake City, Utah, USA.ORCID http://orcid.org/0000-0003-3808-0811
Ella J EatonDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Kanut LaoharaweeDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Jae-Woong ChangDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA mori0164@umn.edu webb0178@umn.edu.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA mori0164@umn.edu webb0178@umn.edu.

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
TRAINING IN HEMOGLOBIN &CELL MEMBRANE RESEARCHT32HL007062 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller, Gregory M Vercellotti · 1985 to 2026
$10.3M
Project 3P01CA254849 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW, MASOPUST, DAVID · 2021 to 2025
$9.4M
TECH CoreU54CA268069 · NCI · UNIVERSITY OF MINNESOTA · PI David J. Odde · 2022 to 2026
$8.2M
SCGE Disease Models Studies Supplement: Evaluation of prime editing for the amelioration of alpha-1-antitrypsin deficiency in murine and porcine models.U24OD026641 · OD · RECOMBINETICS, INC. · PI CARLSON, DANIEL FRED · 2018 to 2022
$4.1M
Activated NK CAR Cells to Cure HIVR01AI161017 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S, SKINNER, PAMELA J · 2021 to 2025
$3.8M
Engineered B Cells as a Universal Platform for the Treatment of EnzymopathiesR01AI146009 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 2020 to 2024
$1.9M
Multiplex Engineered Human Lymphocytes for Therapeutic Protein DeliveryR21AI163731 · NIAID · UNIVERSITY OF MINNESOTA · PI WEBBER, BEAU RICHARD · 2021 to 2022
$426k
Determining the cell of origin in Ewing sarcoma through genomic analysisR21CA237789 · NCI · UNIVERSITY OF MINNESOTA · PI SPECTOR, LOGAN G., WEBBER, BEAU RICHARD · 2020 to 2021
$396k
NCI NIH HHS P01 CA254849NCI NIH HHS P30 CA077598NCI NIH HHS P50 CA136393NCI NIH HHS R21 CA237789NCI NIH HHS U54 CA268069NHLBI NIH HHS T32 HL007062NIAID NIH HHS R01 AI146009NIAID NIH HHS R01 AI161017NIAID NIH HHS R21 AI163731NIH HHS U24 OD026641
6 · The paper itself

Abstract

backgroundNatural killer (NK) cells' unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated only moderate responses against cancer in clinical trials.

methodsAdvanced genome engineering may thus be used to unlock their full potential. Multiplex genome editing with CRISPR/Cas9 base editors (BEs) has been used to enhance T cell function and has already entered clinical trials but has not been reported in human NK cells. Here, we report the first application of BE in primary NK cells to achieve both loss-of-function and gain-of-function mutations.

resultsWe observed highly efficient single and multiplex base editing, resulting in significantly enhanced NK cell function in vitro and in vivo. Next, we combined multiplex BE with non-viral

conclusionsThe use of concomitant non-viral transposon engineering with multiplex base editing thus represents a highly versatile and efficient platform to generate CAR-NK products for cell-based immunotherapy and affords the flexibility to tailor multiple gene edits to maximize the effectiveness of the therapy for the cancer type being treated.

Indexed as

Gene EditingImmunotherapy, AdoptiveKiller Cells, NaturalReceptors, Chimeric AntigenAnimalsCRISPR-Cas SystemsHumansMiceReceptors, Chimeric AntigenChimeric antigen receptor - CARGene therapyHematologic MalignanciesImmunotherapyNatural killer - NK

Identifiers

PMID40341025
PMCPMC12067936

What OpenQuestion holds

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LicenceCC BY-NC
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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.