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 mate...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Tehran University of Medical Sciences
2022-12-01
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| Series: | Iranian Journal of Allergy, Asthma and Immunology |
| Subjects: | |
| Online Access: | https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3613 |
| Summary: | 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.
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| ISSN: | 1735-1502 1735-5249 |