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Process development for adoptive cell therapy in academia: a pipeline for clinical-scale manufacturing of multiple TCR-T cell products

Cellular immunotherapies based on T cell receptor (TCR) transfer are promising approaches for the treatment of cancer and chronic viral infections. The discovery of novel receptors is expanding considerably; however, the clinical development of TCR-T cell therapies still lags. Here we provide a pipe...

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Main Authors: Silva, Daniela (Author) , Chrobok, Michael (Author) , Rovesti, Giulia (Author) , Healy, Katie (Author) , Wagner, Arnika Kathleen (Author) , Maravelia, Panagiota (Author) , Gatto, Francesca (Author) , Mazza, Massimiliano (Author) , Mazzotti, Lucia (Author) , Lohmann, Volker (Author) , Sällberg Chen, Margaret (Author) , Sällberg, Matti (Author) , Buggert, Marcus (Author) , Pasetto, Anna (Author)
Format: Article (Journal)
Language:English
Published: 16 June 2022
In: Frontiers in immunology
Year: 2022, Volume: 13, Pages: 1-16
ISSN:1664-3224
DOI:10.3389/fimmu.2022.896242
Online Access:Resolving-System, kostenfrei, Volltext: https://doi.org/10.3389/fimmu.2022.896242
Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.896242
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Author Notes:Daniela Nascimento Silva, Michael Chrobok, Giulia Rovesti, Katie Healy, Arnika Kathleen Wagner, Panagiota Maravelia, Francesca Gatto, Massimiliano Mazza, Lucia Mazzotti, Volker Lohmann, Margaret Sällberg Chen, Matti Sällberg, Marcus Buggert and Anna Pasetto
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Summary:Cellular immunotherapies based on T cell receptor (TCR) transfer are promising approaches for the treatment of cancer and chronic viral infections. The discovery of novel receptors is expanding considerably; however, the clinical development of TCR-T cell therapies still lags. Here we provide a pipeline for process development and clinical-scale manufacturing of TCR-T cells in academia. We utilized two TCRs specific for hepatitis C virus (HCV) as models because of their marked differences in avidity and functional profile in TCR-redirected cells. With our clinical-scale pipeline, we reproduced the functional profile associated with each TCR. Moreover, the two TCR-T cell products demonstrated similar yield, purity, transduction efficiency as well as phenotype. The TCR-T cell products had a highly reproducible yield of over 1.4 × 109 cells, with an average viability of 93%; 97.8-99% of cells were CD3+, of which 47.66 ± 2.02% were CD8+ T cells; the phenotype was markedly associated with central memory (CD62L+CD45RO+) for CD4+ (93.70 ± 5.23%) and CD8+ (94.26 ± 4.04%). The functional assessments in 2D and 3D cell culture assays showed that TCR-T cells mounted a polyfunctional response to the cognate HCV peptide target in tumor cell lines, including killing. Collectively, we report a solid strategy for the efficient large-scale manufacturing of TCR-T cells.
Item Description:Gesehen am 29.07.2022
Physical Description:Online Resource
ISSN:1664-3224
DOI:10.3389/fimmu.2022.896242

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