Soluble and Immobilized Anti-CD3/28 Distinctively Expand and Differentiate Primary Human T Cells : An Implication for Adoptive T Cell Therapy
Cell-based cancer therapies have led to a paradigm shift in the treatment of patients with various cancers. To date, a vast majority of cancer immunotherapies have used genetically engineered T cells to target tumors. Stimulation and ex vivo expansion of T cells, as one of the crucial starting materials for T cell manufacturing, have always been a critical part of adoptive T-cell therapy (ACT). Typically, anti-CD3 and anti-CD28 monoclonal antibodies (mAbs) along with interleukin-2 (IL-2), through transducing signals one, two, and three, respectively, are essential for in vitro T cell activation. Terminal differentiation and replicative senescence are the main barriers of the ACTs during the manufacturing of engineered T cells ex vivo.In this study, we aimed to compare the T cell activation protocol that we developed in our lab (soluble anti-CD3/28 mAbs) with a common T cell activation protocol (immobilized anti-CD3/soluble anti-CD28) in terms of T cell expansion, activation, immunophenotype, and cellular fate. We observed that T cells were equally expanded in both protocols. Notably, our modified protocol promoted the outgrowth of CD8+ T cells postactivation. Concerning the low concentrations of both soluble anti-CD3 and anti-CD28, the modified protocol could significantly enrich memory T cell subsets. In conclusion, our data demonstrated that the soluble CD3/28 mAbs protocol is cost-effective and more efficient for generating more potent T cells, thereby expecting a better therapeutic outcome.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Iranian journal of allergy, asthma, and immunology - 21(2022), 6 vom: 24. Dez., Seite 630-637 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Soltantoye, Tahereh [VerfasserIn] |
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| Links: |
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| Themen: |
Adoptive cellular therapy |
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| Anmerkungen: |
Date Completed 18.01.2023 Date Revised 18.01.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.18502/ijaai.v21i6.11521 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351509631 |
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| 245 | 1 | 0 | |a Soluble and Immobilized Anti-CD3/28 Distinctively Expand and Differentiate Primary Human T Cells |b An Implication for Adoptive T Cell Therapy |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Cell-based cancer therapies have led to a paradigm shift in the treatment of patients with various cancers. To date, a vast majority of cancer immunotherapies have used genetically engineered T cells to target tumors. Stimulation and ex vivo expansion of T cells, as one of the crucial starting materials for T cell manufacturing, have always been a critical part of adoptive T-cell therapy (ACT). Typically, anti-CD3 and anti-CD28 monoclonal antibodies (mAbs) along with interleukin-2 (IL-2), through transducing signals one, two, and three, respectively, are essential for in vitro T cell activation. Terminal differentiation and replicative senescence are the main barriers of the ACTs during the manufacturing of engineered T cells ex vivo.In this study, we aimed to compare the T cell activation protocol that we developed in our lab (soluble anti-CD3/28 mAbs) with a common T cell activation protocol (immobilized anti-CD3/soluble anti-CD28) in terms of T cell expansion, activation, immunophenotype, and cellular fate. We observed that T cells were equally expanded in both protocols. Notably, our modified protocol promoted the outgrowth of CD8+ T cells postactivation. Concerning the low concentrations of both soluble anti-CD3 and anti-CD28, the modified protocol could significantly enrich memory T cell subsets. In conclusion, our data demonstrated that the soluble CD3/28 mAbs protocol is cost-effective and more efficient for generating more potent T cells, thereby expecting a better therapeutic outcome | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adoptive cellular therapy | |
| 650 | 4 | |a Immobilized antibodies | |
| 650 | 4 | |a Lymphocyte activation | |
| 650 | 4 | |a Memory phenotype | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a CD28 Antigens |2 NLM | |
| 650 | 7 | |a CD3 Complex |2 NLM | |
| 650 | 7 | |a Interleukin-2 |2 NLM | |
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| 700 | 1 | |a Mirzaei, Hamid Reza |e verfasserin |4 aut | |
| 700 | 1 | |a Hadjati, Jamshid |e verfasserin |4 aut | |
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