Poliovirus receptor-based chimeric antigen receptor T cells combined with NK-92 cells exert potent activity against glioblastoma
© The Author(s) 2023. Published by Oxford University Press..
BACKGROUND: Poliovirus receptor interacts with 3 receptors: T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif, CD96, and DNAX accessory molecule 1, which are predominantly expressed on T cells and natural killer (NK) cells. Many solid tumors, including IDH wild-type glioblastoma, have been reported to overexpress poliovirus receptor, and this overexpression is associated with poor prognosis. However, there are no preclinical or clinical trials investigating the use of cell-based immunotherapies targeting poliovirus receptor in IDH wild-type glioblastoma.
METHODS: We analyzed poliovirus receptor expression in transcriptome sequencing databases and specimens from IDH wild-type glioblastoma patients. We developed poliovirus receptor targeting chimeric antigen receptor T cells using lentivirus. The antitumor activity of chimeric antigen receptor T cells was demonstrated in patient-derived glioma stem cells, intracranial and subcutaneous mouse xenograft models.
RESULTS: We verified poliovirus receptor expression in primary glioma stem cells, surgical specimens from IDH wild-type glioblastoma patients, and organoids. Accordingly, we developed poliovirus receptor-based second-generation chimeric antigen receptor T cells. The antitumor activity of chimeric antigen receptor T cells was demonstrated in glioma stem cells and xenograft models. Tumor recurrence occurred in intracranial xenograft models because of antigen loss. The combinational therapy of tyrosine-based inhibitory motif extracellular domain-based chimeric antigen receptor T cells and NK-92 cells markedly suppressed tumor recurrence and prolonged survival.
CONCLUSIONS: Poliovirus receptor-based chimeric antigen receptor T cells were capable of killing glioma stem cells and suppressing tumor recurrence when combined with NK-92 cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:116 |
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| Enthalten in: |
Journal of the National Cancer Institute - 116(2024), 3 vom: 07. März, Seite 389-400 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pan, Changqing [VerfasserIn] |
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| Links: |
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| Themen: |
42HK56048U |
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| Anmerkungen: |
Date Completed 08.03.2024 Date Revised 09.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jnci/djad226 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364357592 |
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| 245 | 1 | 0 | |a Poliovirus receptor-based chimeric antigen receptor T cells combined with NK-92 cells exert potent activity against glioblastoma |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press. | ||
| 520 | |a BACKGROUND: Poliovirus receptor interacts with 3 receptors: T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif, CD96, and DNAX accessory molecule 1, which are predominantly expressed on T cells and natural killer (NK) cells. Many solid tumors, including IDH wild-type glioblastoma, have been reported to overexpress poliovirus receptor, and this overexpression is associated with poor prognosis. However, there are no preclinical or clinical trials investigating the use of cell-based immunotherapies targeting poliovirus receptor in IDH wild-type glioblastoma | ||
| 520 | |a METHODS: We analyzed poliovirus receptor expression in transcriptome sequencing databases and specimens from IDH wild-type glioblastoma patients. We developed poliovirus receptor targeting chimeric antigen receptor T cells using lentivirus. The antitumor activity of chimeric antigen receptor T cells was demonstrated in patient-derived glioma stem cells, intracranial and subcutaneous mouse xenograft models | ||
| 520 | |a RESULTS: We verified poliovirus receptor expression in primary glioma stem cells, surgical specimens from IDH wild-type glioblastoma patients, and organoids. Accordingly, we developed poliovirus receptor-based second-generation chimeric antigen receptor T cells. The antitumor activity of chimeric antigen receptor T cells was demonstrated in glioma stem cells and xenograft models. Tumor recurrence occurred in intracranial xenograft models because of antigen loss. The combinational therapy of tyrosine-based inhibitory motif extracellular domain-based chimeric antigen receptor T cells and NK-92 cells markedly suppressed tumor recurrence and prolonged survival | ||
| 520 | |a CONCLUSIONS: Poliovirus receptor-based chimeric antigen receptor T cells were capable of killing glioma stem cells and suppressing tumor recurrence when combined with NK-92 cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Receptors, Chimeric Antigen |2 NLM | |
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| 700 | 1 | |a Wang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Zhiyi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Mingchen |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Yiyun |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Zhongfang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guanzhang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
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