The Expression of LDL-R in CD8+ T Cells Serves as an Early Assessment Parameter for the Production of TCR-T Cells
Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..
BACKGROUND/AIM: The quantity and the phenotypes of desired T cell receptor engineered T (TCR-T) cells in the final cell product determine their in vivo anti-tumor efficacy. Optimization of key steps in the TCR-T cell production process, such as T cell activation, has been shown to improve cell quality.
MATERIALS AND METHODS: Using a modified TCR (mTCR) derived from mice transducing PBMCs, we assessed the proportions of low-density lipoprotein receptor (LDL-R) and mTCR expressing cells under the various activation conditions of CD3/CD28-Dynabeads or OKT3 via flow cytometry.
RESULTS: We demonstrate that the proportion of T cells expressing LDL-R post activation is positively correlated with the percentage of mTCR+CD8+ T cells with their less differentiated subtypes in the final product. In addition, we show that shifting the CD3/CD28-Dynabeads activation duration from a typical 48 h to 24 h can significantly increase the production of the desired mTCR+CD8+ T cells. Importantly, the percentages of TCR-T cells with less-differentiated phenotypes, namely mTCR central memory T cells (TCM), were found to be preserved with markedly higher efficiency when T cell activation was optimized.
CONCLUSION: Our findings suggest that the proportion of LDL-R+ T cells may serve as an early assessment parameter for evaluating TCR-T cell quality, possibly facilitating the functional and economical improvement of current adoptive therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
In vivo (Athens, Greece) - 37(2023), 6 vom: 31. Nov., Seite 2480-2489 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Y I [VerfasserIn] |
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| Links: |
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| Themen: |
CD28 Antigens |
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| Anmerkungen: |
Date Completed 01.11.2023 Date Revised 04.11.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.21873/invivo.13355 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. | ||
| 520 | |a BACKGROUND/AIM: The quantity and the phenotypes of desired T cell receptor engineered T (TCR-T) cells in the final cell product determine their in vivo anti-tumor efficacy. Optimization of key steps in the TCR-T cell production process, such as T cell activation, has been shown to improve cell quality | ||
| 520 | |a MATERIALS AND METHODS: Using a modified TCR (mTCR) derived from mice transducing PBMCs, we assessed the proportions of low-density lipoprotein receptor (LDL-R) and mTCR expressing cells under the various activation conditions of CD3/CD28-Dynabeads or OKT3 via flow cytometry | ||
| 520 | |a RESULTS: We demonstrate that the proportion of T cells expressing LDL-R post activation is positively correlated with the percentage of mTCR+CD8+ T cells with their less differentiated subtypes in the final product. In addition, we show that shifting the CD3/CD28-Dynabeads activation duration from a typical 48 h to 24 h can significantly increase the production of the desired mTCR+CD8+ T cells. Importantly, the percentages of TCR-T cells with less-differentiated phenotypes, namely mTCR central memory T cells (TCM), were found to be preserved with markedly higher efficiency when T cell activation was optimized | ||
| 520 | |a CONCLUSION: Our findings suggest that the proportion of LDL-R+ T cells may serve as an early assessment parameter for evaluating TCR-T cell quality, possibly facilitating the functional and economical improvement of current adoptive therapy | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Han, Xiao-Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ying-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Si-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun-Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ting-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Ai-Shun |e verfasserin |4 aut | |
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