Evidence map›Paper›PMID 41744817›Full record

ArticleCells2026

Engineering Bi-Specific CAR-NK Cells to Restore Antibody-Dependent Cellular Cytotoxicity in Solid Tumors.

Jee Young Chung, Jung Eun Kim, Daseuri Cha, Hye Jin Lee, Els Verhoeyen, Hee Jung An, Jung Eun Park

Abstract read
In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Jee Young ChungCHA R&D Institute (CHARI), Seongnam 13488, Republic of Korea.
Jung Eun KimCHA R&D Institute (CHARI), Seongnam 13488, Republic of Korea.
Daseuri ChaDepartment of Biomaterials Engineering, CHA University, 120, Haeryong-ro, Pocheonsi 11160, Republic of Korea.ORCID 0009-0006-7364-9005
Hye Jin LeeCHA R&D Institute (CHARI), Seongnam 13488, Republic of Korea.
Els VerhoeyenCentre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR 5308, 69007 Lyon, France.ORCID 0000-0001-9224-5491
Hee Jung AnCha Bundang Medical Center, Cha University School of Medicine, Seongnam 13496, Republic of Korea.
Jung Eun ParkCHA R&D Institute (CHARI), Seongnam 13488, Republic of Korea.

Funding

National Research Foundation of Korea (NRF) RS-2023-00247525
6 · The paper itself

Abstract

Natural Killer (NK) cell-based immunotherapy relies on CD16-mediated Antibody-Dependent Cellular Cytotoxicity (ADCC), yet the ovarian tumor microenvironment (TME) severely compromises this function via Transforming Growth Factor-beta (TGF-β). This study investigated the molecular mechanisms driving this suppression and evaluated a bi-specific Chimeric Antigen Receptor (CAR) strategy to overcome this hurdle. Primary PBNK cells exposed to TGF-β showed sustained canonical SMAD2 phosphorylation, accompanied by a marked reduction in activating receptors such as CD16 and NKG2D and an increase in exhaustion markers such as PD-1. Functionally, these phenotypic alterations led to failed infiltration and cytotoxicity in vitro and within ovarian cancer-derived spheroids. To overcome this limitation, we engineered NK-92 cells with a bi-specific CAR-targeting Folate Receptor Alpha (FRα) and CD16. While TGF-β typically impairs NK cell function, our armed CAR-NK cells successfully infiltrated tumoroids and synergized with Trastuzumab to induce potent ADCC-mediated lysis. Our findings define the TGF-β/SMAD2 axis as a central driver of NK cell dysfunction in ovarian cancer and demonstrate that bi-specific CAR-NK platforms offer a robust therapeutic solution to bypass TME-induced suppression and restore antibody-mediated tumor suppression.

Indexed as

Antibody-Dependent Cell CytotoxicityKiller Cells, NaturalOvarian NeoplasmsReceptors, Chimeric AntigenAnimalsCell Line, TumorFemaleHumansNK Cell Lectin-Like Receptor Subfamily KReceptors, IgGSmad2 ProteinTransforming Growth Factor betaTrastuzumabTumor MicroenvironmentNK Cell Lectin-Like Receptor Subfamily KReceptors, Chimeric AntigenReceptors, IgGSmad2 ProteinTransforming Growth Factor betaTrastuzumabADCCCAR-NKCD16natural killer cells (NK cells)ovarian cancerTGF-β

Identifiers

PMID41744817
PMCPMC12939953

What OpenQuestion holds

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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.