Evidence map›Paper›PMID 41650952›Full record

ArticleCell reports. Medicine2026

Programmable iPSC-derived CAR-NK vesicles remodel the immune microenvironment and eradicate tumors.

Hao Zhang, Shenglong Li, Chongzhong Liu, Xiangdong Gongye, Han Li, Yiyi Ji, Cheng-Wei Ju, Wenzhen Jia, Xing Niu, Yujing Guan and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 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.

  1. Article
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  4. Review
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  7. Review
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

13 authors.

Hao ZhangDepartment of Organ transplant, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China; Second Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
Shenglong LiSecond Ward of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China; The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang 110042, Liaoning, China; Institute of Cancer Medicine, Faculty of Medicine, Dalian University of Technology, Dalian 116024, Liaoning, China.
Chongzhong LiuSecond Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
Xiangdong GongyeDepartment of Chemistry and Molecular Biology, Sahlgrenska Akademin, Göteborg University, Gothenburg, Vastra Gotalands, Sweden.
Han LiDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
Yiyi JiDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA; Department of Medicine, Duke University School of Medicine, Duke University, Durham, NC, USA.
Cheng-Wei JuDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
Wenzhen JiaDepartment of Information Management and Information Systems, School of Business, Shandong Normal University, Jinan, Shandong, China.
Xing NiuChina Medical University, Shenyang, Liaoning, China.
Yujing GuanSecond Ward of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China; The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang 110042, Liaoning, China; Institute of Cancer Medicine, Faculty of Medicine, Dalian University of Technology, Dalian 116024, Liaoning, China.
Xiangyu ZhaiSecond Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: xiangyuzhai@email.sdu.edu.cn.
Bin JinSecond Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: jinbin@sdu.edu.cn.
Peng XiaDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA; Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, P.R. China. Electronic address: pengxia@uchicago.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) cell therapy transforms hematologic cancer treatment but remains limited in solid tumors due to stromal barriers and an immunosuppressive tumor microenvironment that restricts immune cell infiltration. To address these barriers, we develop a cell-free therapeutic platform based on CAR-engineered induced pluripotent stem cell (iPSC)-derived natural killer (NK) extracellular vesicles (CAR-iNEVs), which retain tumor-targeting capability without reliance on live-cell delivery. CAR-iNEV demonstrates potent antitumor activity and excellent tolerability across multiple xenograft and patient-derived models. Mechanistically, CAR-iNEV directly eliminates tumor cells and remodels the tumor microenvironment by promoting pro-inflammatory macrophage polarization, thereby enhancing host innate antitumor immunity. CAR-iNEV also functions cooperatively with immune checkpoint blockade, and combined treatment with CAR-iNEV and CD47 inhibition increases tumor clearance and induces long-term immunological memory in surviving mice. These findings support the therapeutic potential of CAR-iNEV for solid tumors through coordinated tumor targeting and immune microenvironment modulation.

Indexed as

Extracellular VesiclesImmunotherapy, AdoptiveInduced Pluripotent Stem CellsKiller Cells, NaturalNeoplasmsReceptors, Chimeric AntigenTumor MicroenvironmentAnimalsCell Line, TumorHumansMiceReceptors, Chimeric Antigencell-free cancer immunotherapyengineered extracellular vesiclesiPSC-derived CAR-NK extracellular vesiclessolid tumor immunotherapytumor microenvironment remodeling

Identifiers

PMID41650952
PMCPMC12923919

What OpenQuestion holds

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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.