Evidence map›Paper›PMID 39523093›Full record

ArticleNan fang yi ke da xue xue bao = Journal of Southern Medical University2024

[Modification with IL-21 and CCL19 enhances killing efficiency and tumor infiltration of NKP30 CAR-T cells in lung cancer].

Z Zhou, S Liu, J Li, M Chen, H Lin, Y Chen, W Chen, J Lin, H Zhou, Q Zheng

Abstract readEnglish Abstract
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Article in Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Z ZhouLaboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
S LiuDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
J LiLaboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
M ChenDepartment of Thoracic Oncology Radiation, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
H LinDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
Y ChenDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
W ChenDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
J LinDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
H ZhouDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
Q ZhengDepartment of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.

methodsThe modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2. The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments. Lactate dehydrogenase (LDH) release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells, and the secretion levels of IFN-γ, IL-21 and CCL19 were determined with enzyme-linked immunospot assay (ELISPOT) and ELISA. A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site, and the fluorescence signals were captured using a fluorescent microscopy.

resultsThe NKP30 ligand B7H6, which was almost undetectable in normal tissues and blood cells, was highly expressed (over 90%) in lung cancer cells. Compared with NKP30 CAR-T cells and conventional T cells, IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells. The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ, IL-21 and CCL19. In the zebrafish models, CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells, but these differences were not statistically significant between the two CAR-T cells.

conclusionModification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.

Indexed as

Chemokine CCL19InterleukinsLung NeoplasmsNatural Cytotoxicity Triggering Receptor 3ZebrafishAnimalsCell Line, TumorHumansImmunotherapy, AdoptiveInterferon-gammaInterleukin-21Receptors, Chimeric AntigenT-LymphocytesCCL19 protein, humanChemokine CCL19Interferon-gammaInterleukin-21InterleukinsNatural Cytotoxicity Triggering Receptor 3NCR3 protein, humanReceptors, Chimeric AntigenCCL19chimeric antigen receptor gene modified-T lymphocytesinterleukin-21lung cancerNKP30

Identifiers

PMID39523093
PMCPMC11526451

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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.