Evidence map›Paper›PMID 40474210›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

CD70 CAR-T cells empowered by TS-2021 through ex vivo transduction show potent antitumor efficacy against glioblastoma.

Sheng Fang, Jiankun Wu, Yida Liu, Peiwen Wang, Guiqiang Yuan, Jiajia Gao, Wenxin Zhang, Junwen Zhang, Fusheng Liu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
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  6. CAR-T cells immunotherapy in the treatment of glioblastoma.Cancer immunology, immunotherapy : CII · 2025
    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

9 authors.

Sheng FangBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Jiankun WuBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Yida LiuBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Peiwen WangBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Guiqiang YuanBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Jiajia GaoBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Wenxin ZhangBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China.
Junwen ZhangBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China. jewzhang@hotmail.com.
Fusheng LiuBrain Tumor Research Center, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, China. liufusheng@ccmu.edu.cn.

Funding

Beijing Municipal Health Commission 11000023T000002044300-3Capital Funds for Health Improvement and Research CFH, 2024-1-1071National Natural Science Foundation of China 52373129
6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR) T-cell therapy has shown limited efficacy in glioblastoma (GBM) due to tumor antigen heterogeneity and the immunosuppressive microenvironment. To address these barriers, we developed a novel combinatorial approach: engineering CAR-T cells with third-generation oncolytic adenoviruses (OAd) to enable targeted viral delivery and sustained immune activation. Unlike conventional OAd administration, this strategy leverages CAR-T cells as tumor-tropic vectors for localized oncolysis and cytokine modulation.

methodsCD70-specific CAR-T cells were transduced with two third-generation OAds (E1B19K/E3-deleted, replication-selective): OAd-GFP (control) or OAd-IL15 (TS-2021), generating CAR-T

resultsIn this study, we found that genetically engineered OAd-GFP can specifically replicate within CAR-T cells and be precisely delivered to GBM through an antigen-specific mechanism. Prolonged antigen stimulation induced T-cell exhaustion, limiting the efficacy of CAR-T therapy. TS-2021-infected CAR-T cells exhibited enhanced expansion and persistence in vitro, with reduced expression of exhaustion markers under sustained antigen stimulation. IL15 autocrine signaling activated JAK-STAT and MAPK-ERK pathways. This process repaired the DNA damage induced by OAd in CAR-T cells and maintained their expansion and persistence. By combining OAd-mediated oncolysis with IL15-driven CAR-T persistence, CAR-T

conclusionsBy integrating IL15-armed OAd into CAR-T cells, we demonstrate a synergistic strategy that simultaneously enhances viral oncolysis, sustains T-cell persistence, and counteracts GBM immunosuppression. This approach addresses both antigenic heterogeneity and microenvironment-driven resistance, providing a translatable paradigm for solid tumor immunotherapy.

Indexed as

Brain NeoplasmsCD27 LigandGlioblastomaImmunotherapy, AdoptiveInterleukin-15Receptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorHumansMiceTransduction, GeneticXenograft Model Antitumor AssaysCD27 LigandCD70 protein, humanInterleukin-15Receptors, Chimeric AntigenCAR-T-cell immunotherapyCD70GlioblastomaIL15Oncolytic adenovirus

Identifiers

PMID40474210
PMCPMC12139114

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.