Evidence map›Paper›PMID 42421037›Full record

ArticleJournal of translational medicine2026

Engineered PD1-NKG2D Dual-CAR NK92 cells broaden antitumor target recognition in preclinical tumor models.

Xinru Jin, Mingfeng Li, Mengjun Wang, Jin Zhao, Zhiyuan Niu, Changjiang Guo, Lingtong Zhi, Norfarazieda Hassan, Wuling Zhu

Abstract read
In one paragraph

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

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0citing papers in PubMed
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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

9 authors.

Xinru JinHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Mingfeng LiHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Mengjun WangHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Jin ZhaoHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Zhiyuan NiuHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Changjiang GuoHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Lingtong ZhiHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China.
Norfarazieda HassanDepartment of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Bertam, 13200, Malaysia. fara.hassan@usm.my.
Wuling ZhuHenan Province Engineering Technology Research Center of Advanced Synbiomedicine and Clinical Innovation Translation, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan, China. wuling_zhu@163.com.

Funding

Henan Provincial Science and Technology Research and Development Joint Fund (Industrial) 235101610047National Natural Science Foundation of China 82003261
6 · The paper itself

Abstract

backgroundTo address challenges such as the complex manufacturing of CAR-T and the immunosuppressive tumor microenvironment (TME), CAR-NK cells offer greater potential as an "off-the-shelf" therapy. To broaden tumor recognition and reduce the risk of immune escape associated with single-target approaches, we developed a single-promoter-driven multicistronic CAR-NK92 system that employs NKG2D for broad recognition of stress ligands and combines a PD1-CAR to reverse PD-L1 inhibitory signaling, thereby significantly enhancing antitumor efficacy.

methodsA multicistronic construct co-expressing PD1-CAR and NKG2D-CAR was generated using a P2A peptide under the control of a single CMV promoter and introduced into NK92 cells. The expression of PD-L1 and MICA/B was screened across multiple tumor cell lines, and the functional robustness of PN-CAR-NK92 cells was evaluated in all models through in vitro cytotoxicity and cytokine secretion assays. The in vivo translational efficacy was further validated using an H1299 xenograft model, with a direct comparison between PN-CAR-NK92 cells and NK92 cells.

resultsThe multicistronic design enabled stable surface co-expression of both receptor modules, providing a structural basis for dual-target functionality. In vitro cytotoxicity assays demonstrated that PN-CAR-NK92 cells maintained robust antitumor activity across tumor cell lines with distinct PD-L1 and MICA/B expression profiles, whereas single-target CAR-NK92 cells displayed more restricted target specificity. These findings suggest that dual-target CAR engineering broadens antigen recognition coverage and may help reduce the limitations associated with single-target antigen dependence. Furthermore, PN-CAR-NK92 cells demonstrated significantly enhanced tumor suppression in the H1299 xenograft model compared with control groups.

conclusionsDual-target PD1/NKG2D CAR-NK92 cells exhibit broadened antitumor activity across tumor cells with distinct ligand-expression profiles and may represent a promising strategy to reduce the limitations associated with single-target CAR therapies.

Indexed as

Genetic EngineeringKiller Cells, NaturalNeoplasmsNK Cell Lectin-Like Receptor Subfamily KProgrammed Cell Death 1 ReceptorReceptors, Chimeric AntigenAnimalsCell Line, TumorFemaleHumansMiceXenograft Model Antitumor AssaysKLRK1 protein, humanNK Cell Lectin-Like Receptor Subfamily KProgrammed Cell Death 1 ReceptorReceptors, Chimeric AntigenCAR-NK92Dual-CARNKG2DPD-1Tumor immunotherapy

Identifiers

PMID42421037
PMCPMC13452103

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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.