Evidence map›Paper›PMID 40855348›Full record

ArticleExperimental hematology & oncology2025

Improving CAR-T cell function through a targeted cytokine delivery system utilizing car target-modified extracellular vesicles.

Yuanyuan Zhang, Meijuan Huang, Shujia Zhang, Tianjiao Liu, Shanwei Ye, Yuhang Cheng, Yang Cao, Liting Chen, Li Zhu, Xueyan Sun and 8 more

Abstract read
In one paragraph

Article in Experimental hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

18 authors.

Yuanyuan Zhang *Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Meijuan Huang *Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shujia ZhangDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tianjiao LiuDepartment of Hematology and Oncology, Ningbo No.2 Hospital, Ningbo, Zhejiang Province, China.
Shanwei YeDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yuhang ChengDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang CaoDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Liting ChenDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li ZhuDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xueyan SunDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Kefeng ShenDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Qian XuDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tongjuan LiDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Dengju LiDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Liang HuangState Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
Wei MuDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lei ZhaoDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. zl103311@tjh.tjmu.edu.cn.
Jue WangDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. juewang@tjh.tjmu.edu.cn.

Funding

Beijing Xisike Clinical Oncology Research Foundation Y-2022YMJN/MS-0005National Natural Science Foundation of China 82100247National Natural Science Foundation of China 82270177
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-T-cell therapy has achieved remarkable clinical success in the treatment of B-cell malignancies; however, its efficacy can be limited by poor T-cell persistence and insufficient antitumor activity in certain cases. Moreover, interleukin-12 (IL-12) is a prominent agent in cancer immunotherapy, but its clinical application is constrained by severe toxicity associated with systemic exposure. In this study, we developed a novel cytokine delivery platform based on CAR target-modified cell-derived extracellular vesicles (EVs) that preferentially bind CAR-T cells to improve CAR-T-cell function. EVs with surface-displayed CD19 and/or IL-12 were successfully generated from HEK-293T cells. Compared with an equivalent concentration of rhIL-12, IL-12 EVs significantly enhanced the effector function of anti-CD19 CAR-T cells in vitro, resulting in increased Interferon-γ (IFN-γ) and TNF-α secretion, cytolytic activity, and T-cell expansion. Additionally, compared with EVs expressing IL-12 alone, EVs co-expressing IL-12 and CD19 (CD19/IL-12 EVs) exhibited superior binding efficiency to CAR-T cells but not to T cells, as indicated by flow cytometry. In xenograft model mice bearing CD19 + Raji tumors, intratumoral injection of CD19/IL-12 EVs resulted in durable antitumor responses and enhanced the in vivo expansion of CAR-T cells, outperforming CD19 EVs, IL-12 EVs and control EVs, without causing systemic toxicity. RNA sequencing (RNA-seq) analysis of CAR-T cells stimulated with EVs suggested that the increased efficacy was driven by IL-12 signaling. These data demonstrate that CAR-targeted modified EVs may serve as targeted cytokine delivery systems for CAR-T cells, offering a safe and effective strategy to augment CAR-T-cell function.

Indexed as

Cellular immunotherapyChimeric antigen receptor T cellExtracellular vesiclesInterleukin-12

Identifiers

PMID40855348
PMCPMC12379361

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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.