Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 14 03 2022
accepted: 13 05 2022
entrez: 5 7 2022
pubmed: 6 7 2022
medline: 7 7 2022
Statut: epublish

Résumé

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 × 10

Identifiants

pubmed: 35784320
doi: 10.3389/fimmu.2022.896242
pmc: PMC9243500
doi:

Substances chimiques

Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

896242

Informations de copyright

Copyright © 2022 Silva, Chrobok, Rovesti, Healy, Wagner, Maravelia, Gatto, Mazza, Mazzotti, Lohmann, Sällberg Chen, Sällberg, Buggert and Pasetto.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Daniela Nascimento Silva (DN)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Michael Chrobok (M)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Giulia Rovesti (G)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Oncology, Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences of Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.

Katie Healy (K)

Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

Arnika Kathleen Wagner (AK)

Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.

Panagiota Maravelia (P)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Francesca Gatto (F)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Massimiliano Mazza (M)

Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Lucia Mazzotti (L)

Immunotherapy, Cell Therapy and Biobank (ITCB), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Volker Lohmann (V)

Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany.

Margaret Sällberg Chen (M)

Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

Matti Sällberg (M)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

Marcus Buggert (M)

Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.

Anna Pasetto (A)

Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

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