Evidence map›Paper›PMID 41821313›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.

Jacob Bridge, Matthew J Johnson, Bibekananda Kar, Jihyun Kim, Sophia Wenthe, Joshua Krueger, Bryce Wick, Mitchell G Kluesner, Andrew T Crane, Jason Bell and 5 more

Abstract read
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Jacob BridgeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Matthew J JohnsonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Bibekananda KarDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Jihyun KimDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Sophia WentheDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Joshua KruegerDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Bryce WickDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Mitchell G KluesnerMolecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98109, USA; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Andrew T CraneDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Jason BellDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Lage von DissenDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Erin StelljesDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Joseph G SkeateDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: webb0178@umn.edu.

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI SCOTT H KAUFMANN · 2009 to 2026
$37.0M
Project 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CASSADY, KEVIN A, CRIPE, TIMOTHY P · 2019 to 2023
$12.1M
Project 3P01CA254849 · NCI · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 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
Deconvoluting the Ewing sarcoma genetic program using ancestry-informed human iPSC modelingR37CA276345 · NCI · UNIVERSITY OF MINNESOTA · PI Beau Richard Webber · 2023 to 2026
$2.2M
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
Human iPSC-Derived Chimeric Antigen Receptor Macrophages to Modulate Inflammation and Combat Tau-Induced PathologyR61AG090358 · NIA · UNIVERSITY OF MINNESOTA · PI Jonathan N Sachs, Beau Richard Webber · 2025 to 2026
$1.5M
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 F30 CA305905NCI NIH HHS P01 CA254849NCI NIH HHS P30 CA077598NCI NIH HHS P50 CA136393NCI NIH HHS R21 CA237789NCI NIH HHS R37 CA276345NCI NIH HHS U54 CA232561NCI NIH HHS U54 CA268069NIAID NIH HHS R01 AI146009NIAID NIH HHS R01 AI161017NIAID NIH HHS R21 AI163731NIA NIH HHS R61 AG090358NIH HHS U24 OD026641
6 · The paper itself

Abstract

Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-major histocompatibility complex-associated antigens on transformed and pathogen-infected cells. In addition to their inability to mediate graft versus host disease, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene-edited chimeric antigen receptor (CAR)-γδ T cells for therapeutic application. Engineered CAR-γδ T cells demonstrate robust functionality in vitro and in vivo. Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo.

Indexed as

Immunotherapy, AdoptiveReceptors, Antigen, T-Cell, gamma-deltaReceptors, Chimeric AntigenT-LymphocytesAnimalsGene EditingHumansMiceReceptors, Antigen, T-Cell, gamma-deltaReceptors, Chimeric Antigenadoptive cell therapybase editingcancer immunotherapychimeric antigen receptorsIL-15 armoringmultiplex genome editingnon-viral engineeringpolyclonal expansiontransposon integrationγδ T cells

Identifiers

PMID41821313
PMCPMC13209012

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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.