Evidence map›Paper›PMID 38368374›Full record

ArticleJournal of translational medicine2024

Combined therapy of CAR-IL-15/IL-15Rα-T cells and GLIPR1 knockdown in cancer cells enhanced anti-tumor effect against gastric cancer.

Jianbin Ye, Qiaoyuan Liu, Yunxuan He, Zhenkun Song, Bao Lin, Zhiwei Hu, Juanyuan Hu, Yunshan Ning, Cheguo Cai, Yan Li

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
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

14 citing papers in PubMed, 14 citations in OpenAlex.

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  8. Human Immune System Reconstitution in NOD/Shi-Life (Basel, Switzerland) · 2025
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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

10 authors at 2 institutions in 1 country.

Jianbin YeSchool of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Qiaoyuan LiuSchool of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Yunxuan HeSchool of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Zhenkun SongShenzhen Beike Biotechnology Co., Ltd., Shenzhen, 518000, Guangdong, People's Republic of China.
Bao LinShenzhen Beike Biotechnology Co., Ltd., Shenzhen, 518000, Guangdong, People's Republic of China.
Zhiwei HuShenzhen Beike Biotechnology Co., Ltd., Shenzhen, 518000, Guangdong, People's Republic of China.
Juanyuan HuShenzhen Beike Biotechnology Co., Ltd., Shenzhen, 518000, Guangdong, People's Republic of China.
Yunshan NingSchool of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. nys@smu.edu.cn.
Cheguo CaiShenzhen Beike Biotechnology Co., Ltd., Shenzhen, 518000, Guangdong, People's Republic of China. cheguo_cai@ucas.ac.cn.
Yan LiSchool of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. luckyan@smu.edu.cn.ORCID 0000-0001-8851-7159
Beike Biotechnology (China) · CNSouthern Medical University · CN

Funding

Basic and Applied basic Research Project of Guangdong Province 2023A1515010084National Key R&D Program of China, Synthetic Biology Research 2019YFA0903802National Natural Science Foundation of China 81971903
6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR) T cell therapy has shown remarkable responses in hematological malignancies with several approved products, but not in solid tumors. Patients suffer from limited response and tumor relapse due to low efficacy of CAR-T cells in the complicated and immunosuppressive tumor microenvironment. This clinical challenge has called for better CAR designs and combined strategies to improve CAR-T cell therapy against tumor changes.

methodsIn this study, IL-15/IL-15Rα was inserted into the extracellular region of CAR targeting mesothelin. In-vitro cytotoxicity and cytokine production were detected by bioluminescence-based killing and ELISA respectively. In-vivo xenograft mice model was used to evaluate the anti-tumor effect of CAR-T cells. RNA-sequencing and online database analysis were used to identify new targets in residual gastric cancer cells after cytotoxicity assay. CAR-T cell functions were detected in vitro and in vivo after GLI Pathogenesis Related 1 (GLIPR1) knockdown in gastric cancer cells. Cell proliferation and migration of gastric cancer cells were detected by CCK-8 and scratch assay respectively after GLIPR1 were overexpressed or down-regulated.

resultsCAR-T cells constructed with IL-15/IL-15Rα (CAR-ss-T) showed significantly improved CAR-T cell expansion, cytokine production and cytotoxicity, and resulted in superior tumor control compared to conventional CAR-T cells in gastric cancer. GLIPR1 was up-regulated after CAR-T treatment and survival was decreased in gastric cancer patients with high GLIPR1 expression. Overexpression of GLIPR1 inhibited cytotoxicity of conventional CAR-T but not CAR-ss-T cells. CAR-T treatment combined with GLIPR1 knockdown increased anti-tumor efficacy in vitro and in vivo.

conclusionsOur data demonstrated for the first time that this CAR structure design combined with GLIPR1 knockdown in gastric cancer improved CAR-T cell-mediated anti-tumor response.

Indexed as

Receptors, Chimeric AntigenStomach NeoplasmsAnimalsCell Line, TumorHumansImmunotherapy, AdoptiveInterleukin-15Membrane ProteinsMiceNeoplasm ProteinsNeoplasm Recurrence, LocalNerve Tissue ProteinsT-LymphocytesTumor MicroenvironmentXenograft Model Antitumor AssaysGLIPR1 protein, humanInterleukin-15Membrane ProteinsNeoplasm ProteinsNerve Tissue ProteinsReceptors, Chimeric AntigenCAR-TCombined therapyGastric cancerGLIPR1IL-15/IL-15RαSolid tumor

Identifiers

PMID38368374
PMCPMC10874561
OpenAlexW4391917903

What OpenQuestion holds

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LicenceCC BY
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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.