A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this r...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S232905011830007X |
| _version_ | 1811300452732502016 |
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| author | Henrieta Fraser Niloufar Safinia Nathali Grageda Sarah Thirkell Katie Lowe Laura J. Fry Cristiano Scottá Andrew Hope Christopher Fisher Rachel Hilton David Game Paul Harden Andrew Bushell Kathryn Wood Robert I. Lechler Giovanna Lombardi |
| author_facet | Henrieta Fraser Niloufar Safinia Nathali Grageda Sarah Thirkell Katie Lowe Laura J. Fry Cristiano Scottá Andrew Hope Christopher Fisher Rachel Hilton David Game Paul Harden Andrew Bushell Kathryn Wood Robert I. Lechler Giovanna Lombardi |
| author_sort | Henrieta Fraser |
| collection | DOAJ |
| description | The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application. This Treg isolation procedure ensured the selection of a pure Treg population that underwent a 300-fold expansion after 36 days of culture, while maintaining a purity of more than 75% CD4+CD25+FOXP3+ cells and a suppressive function of above 80%. Furthermore, we report the successful cryopreservation of the final product, demonstrating the maintenance of phenotype and function. The process outlined in this manuscript has been implemented in the ONE study, a multicenter phase I/IIa clinical trial in which cellular therapy is investigated in renal transplantation. |
| first_indexed | 2024-04-13T06:51:22Z |
| format | Article |
| id | doaj.art-85e919f3eff5464fb7314ee3c37abc73 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-13T06:51:22Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-85e919f3eff5464fb7314ee3c37abc732022-12-22T02:57:23ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012018-03-018C19820910.1016/j.omtm.2018.01.006A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical TrialsHenrieta Fraser0Niloufar Safinia1Nathali Grageda2Sarah Thirkell3Katie Lowe4Laura J. Fry5Cristiano Scottá6Andrew Hope7Christopher Fisher8Rachel Hilton9David Game10Paul Harden11Andrew Bushell12Kathryn Wood13Robert I. Lechler14Giovanna Lombardi15Division of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKThe Department of Nephrology and Transplantation, Guy’s Hospital, Guy’s and St. Thomas NHS Foundation TrustThe Department of Nephrology and Transplantation, Guy’s Hospital, Guy’s and St. Thomas NHS Foundation TrustOxford Transplant Centre, Oxford, UKTransplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UKTransplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKDivision of Transplantation, Immunology and Mucosal Biology, King’s College London, London, UKThe concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application. This Treg isolation procedure ensured the selection of a pure Treg population that underwent a 300-fold expansion after 36 days of culture, while maintaining a purity of more than 75% CD4+CD25+FOXP3+ cells and a suppressive function of above 80%. Furthermore, we report the successful cryopreservation of the final product, demonstrating the maintenance of phenotype and function. The process outlined in this manuscript has been implemented in the ONE study, a multicenter phase I/IIa clinical trial in which cellular therapy is investigated in renal transplantation.http://www.sciencedirect.com/science/article/pii/S232905011830007XTregsGMP processclinical trialscell therapyONE studysolid organ transplantation |
| spellingShingle | Henrieta Fraser Niloufar Safinia Nathali Grageda Sarah Thirkell Katie Lowe Laura J. Fry Cristiano Scottá Andrew Hope Christopher Fisher Rachel Hilton David Game Paul Harden Andrew Bushell Kathryn Wood Robert I. Lechler Giovanna Lombardi A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials Molecular Therapy: Methods & Clinical Development Tregs GMP process clinical trials cell therapy ONE study solid organ transplantation |
| title | A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials |
| title_full | A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials |
| title_fullStr | A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials |
| title_full_unstemmed | A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials |
| title_short | A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials |
| title_sort | rapamycin based gmp compatible process for the isolation and expansion of regulatory t cells for clinical trials |
| topic | Tregs GMP process clinical trials cell therapy ONE study solid organ transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S232905011830007X |
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