Evidence map›Paper›PMID 31704085›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

A Genetically Engineered Primary Human Natural Killer Cell Platform for Cancer Immunotherapy.

Emily J Pomeroy, John T Hunzeker, Mitchell G Kluesner, Walker S Lahr, Branden A Smeester, Margaret R Crosby, Cara-Lin Lonetree, Kenta Yamamoto, Laura Bendzick, Jeffrey S Miller and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

136 citing papers in PubMed, 178 citations in OpenAlex.

  1. Article
  2. Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026
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  10. Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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  13. Article
  14. Article
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  19. Challenges and opportunities of human iPSC-derived NK as "Off-the-shelf" cellular therapies.Journal of experimental & clinical cancer research : CR · 2025
    Review
  20. Review

76 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

16 authors at 2 institutions in 1 country.

Emily J PomeroyDepartment 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.
John T HunzekerDepartment 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 KluesnerDepartment 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.
Walker S LahrDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Branden A SmeesterDepartment 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.
Margaret R CrosbyDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Cara-Lin LonetreeDepartment 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.
Kenta YamamotoDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Laura BendzickDepartment of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA.
Jeffrey S MillerDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.
Melissa A GellerMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA.
Bruce WalcheckDepartment of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55455, USA.
Martin FelicesMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Medicine, Division of Hematology, Oncology, and Transplantation, 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.
Timothy K StarrMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Department of Obstetrics, Gynecology, and Women's Health, 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. Electronic address: mori0164@umn.edu.
University of Minnesota · USUniversity of Minnesota Medical Center · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller · 1998 to 2026
$100.4M
Project 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CRIPE, TIMOTHY P · 2019 to 2023
$12.1M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
Expression of recombinant Fc receptors by engineered NK cells to enhance cancer cell killingR01CA203348 · NCI · UNIVERSITY OF MINNESOTA · PI WALCHECK, BRUCE K, WU, JIANMING · 2016 to 2025
$4.4M
Genetically Modified Natural Killer Cells for Cancer ImmunotherapyR21CA216652 · NCI · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 2018 to 2019
$362k
NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA203348NCI NIH HHS R21 CA216652NCI NIH HHS U54 CA232561NIAID NIH HHS T32 AI007313
6 · The paper itself

Abstract

Enhancing natural killer (NK) cell cytotoxicity by blocking inhibitory signaling could lead to improved NK-based cancer immunotherapy. Thus, we have developed a highly efficient method for editing the genome of human NK cells using CRISPR/Cas9 to knock out inhibitory signaling molecules. Our method efficiently edits up to 90% of primary peripheral blood NK cells. As a proof-of-principle we demonstrate highly efficient knockout of ADAM17 and PDCD1, genes that have a functional impact on NK cells, and demonstrate that these gene-edited NK cells have significantly improved activity, cytokine production, and cancer cell cytotoxicity. Furthermore, we were able to expand cells to clinically relevant numbers, without loss of activity. We also demonstrate that our CRISPR/Cas9 method can be used for efficient knockin of genes by delivering homologous recombination template DNA using recombinant adeno-associated virus serotype 6 (rAAV6). Our platform represents a feasible method for generating engineered primary NK cells as a universal therapeutic for cancer immunotherapy.

Indexed as

ADAM17 ProteinAdoptive TransferAnimalsCell EngineeringCRISPR-Cas SystemsCytotoxicity, ImmunologicDependovirusFemaleGene Knockout TechniquesGenetic EngineeringHealthy VolunteersHumansK562 CellsKiller Cells, NaturalMiceMice, Inbred NODADAM17 ProteinADAM17 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorADAM17CRISPRimmunotherapyNK cellsPD1

Identifiers

PMID31704085
PMCPMC6953961
OpenAlexW2980981340

What OpenQuestion holds

Textmetadata
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.