Evidence map›Paper›PMID 40456445›Full record

ArticleJournal of advanced research2026

Enhancement of NK cell activity via DNA-sensing inhibition by Poxin transgene.

Ling-Zu Kong, Seok-Min Kim, Soo Yun Lee, In-Hwan Jang, Chunli Wang, Seona Jo, Se-Chan Oh, Sunyoung Lee, Ji Hyun Kim, Kee K Kim and 1 more

Abstract read
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

2 citing papers in PubMed.

  1. Review
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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

11 authors.

Ling-Zu KongCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Republic of Korea.
Seok-Min KimCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Soo Yun LeeCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
In-Hwan JangCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Chunli WangKey Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
Seona JoCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; KRIBB School of Advanced Bioconvergence, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
Se-Chan OhCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Sunyoung LeeCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Ji Hyun KimCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; KRIBB School of Advanced Bioconvergence, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
Kee K KimDepartment of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Republic of Korea.
Tae-Don KimCenter for Gene and Cell Therapy, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea; KRIBB School of Advanced Bioconvergence, University of Science and Technology (UST), Daejeon 34113, Republic of Korea; Biomedical Mathematics Group, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea; Department of Biopharmaceutical Convergence, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: tdkim@kribb.re.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionNatural Killer (NK) cell therapy has shown strong potential for cancer treatment; however, NK cell efficacy is limited by their short lifespan and suppression within the tumor microenvironment. One factor contributing to this suppression may be the activation of the cyclic GMP-AMP synthase (cGAS) pathway. Since the discovery of cGAS as a DNA sensor, there has been renewed interest in DNA sensing mechanisms, although the role of DNA sensing-mediated innate immune responses on NK cells remains unclear. Poxin, a protein derived from DNA viruses, is known to degrade the cGAS signaling product cyclic GMP-AMP (cGAMP) and could potentially alleviate DNA sensing-related stress in NK cells.

objectivesThis study aims to investigate whether Poxin expression can inhibit DNA sensing pathways in NK cells, thereby enhancing their cytotoxic function and anti-tumor activity.

methodsWe generated NK-92 cells expressing a Poxin transgene and evaluated their response to DNA sensing activation. The cGAS-STING pathway was stimulated through either exogenous plasmid transfection or irradiation to induce endogenous double-stranded DNA (dsDNA). We assessed NK-92 and umbilical cord blood derived primary NK (pNK) cells activity through cytotoxicity assay and analysis of perforin and granzyme B expression levels, performed RNA-seq analysis to explore the mechanism and conducted functional assays to evaluate anti-tumor efficacy of NK-92 and chimeric antigen receptors (CAR)-NK-92 cells.

resultsPoxin expression significantly inhibited the cGAS-STING pathway, reducing activation in response to both plasmid transfection and irradiation-induced dsDNA. RNA-seq analysis indicated increased levels of cytotoxic mediators, including perforin and granzyme B, in Poxin-expressing NK-92 cells. Furthermore, these transgenic NK-92/CAR-NK-92 cells exhibited enhanced anti-tumor activity compared to controls.

conclusionPoxin effectively suppresses DNA sensing-mediated innate immunity in NK cells, enhancing their cytotoxicity and anti-tumor effectiveness.

Indexed as

DNAKiller Cells, NaturalViral ProteinsCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseCytotoxicity, ImmunologicHumansImmunity, InnateMembrane ProteinsNucleotides, CyclicNucleotidyltransferasesSignal TransductionSTING ProteinTransgenescGAS protein, humancyclic guanosine monophosphate-adenosine monophosphateCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNAMembrane ProteinsNucleotides, CyclicNucleotidyltransferasesSTING1 protein, humanSTING ProteinViral ProteinsCell therapyDNA sensingNatural killer cellsPoxin

Identifiers

PMID40456445
PMCPMC12957823

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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.