Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing ba...

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Autores principales:	Joanna Balcerek, Brian R. Shy, Amy L. Putnam, Lisa M. Masiello, Angela Lares, Florinna Dekovic, Luis Acevedo, Michael R. Lee, Vinh Nguyen, Weihong Liu, Sreenivasan Paruthiyil, Jingying Xu, Ashley S. Leinbach, Jeffrey A. Bluestone, Qizhi Tang, Jonathan H. Esensten
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	regulatory T cell manufacturing cGMP ex vivo expansion cellular therapy regulatory T cells Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/4fbc3387d354494ba9daa3d9eab90fba
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spelling	oai:doaj.org-article:4fbc3387d354494ba9daa3d9eab90fba2021-11-18T06:30:13ZPolyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience1664-322410.3389/fimmu.2021.744763https://doaj.org/article/4fbc3387d354494ba9daa3d9eab90fba2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.744763/fullhttps://doaj.org/toc/1664-3224We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.Joanna BalcerekBrian R. ShyAmy L. PutnamLisa M. MasielloAngela LaresFlorinna DekovicLuis AcevedoMichael R. LeeVinh NguyenWeihong LiuSreenivasan ParuthiyilJingying XuAshley S. LeinbachJeffrey A. BluestoneJeffrey A. BluestoneQizhi TangQizhi TangJonathan H. EsenstenFrontiers Media S.A.articleregulatory T cell manufacturingcGMPex vivo expansioncellular therapyregulatory T cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	regulatory T cell manufacturing cGMP ex vivo expansion cellular therapy regulatory T cells Immunologic diseases. Allergy RC581-607
spellingShingle	regulatory T cell manufacturing cGMP ex vivo expansion cellular therapy regulatory T cells Immunologic diseases. Allergy RC581-607 Joanna Balcerek Brian R. Shy Amy L. Putnam Lisa M. Masiello Angela Lares Florinna Dekovic Luis Acevedo Michael R. Lee Vinh Nguyen Weihong Liu Sreenivasan Paruthiyil Jingying Xu Ashley S. Leinbach Jeffrey A. Bluestone Jeffrey A. Bluestone Qizhi Tang Qizhi Tang Jonathan H. Esensten Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
description	We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.
format	article
author	Joanna Balcerek Brian R. Shy Amy L. Putnam Lisa M. Masiello Angela Lares Florinna Dekovic Luis Acevedo Michael R. Lee Vinh Nguyen Weihong Liu Sreenivasan Paruthiyil Jingying Xu Ashley S. Leinbach Jeffrey A. Bluestone Jeffrey A. Bluestone Qizhi Tang Qizhi Tang Jonathan H. Esensten
author_facet	Joanna Balcerek Brian R. Shy Amy L. Putnam Lisa M. Masiello Angela Lares Florinna Dekovic Luis Acevedo Michael R. Lee Vinh Nguyen Weihong Liu Sreenivasan Paruthiyil Jingying Xu Ashley S. Leinbach Jeffrey A. Bluestone Jeffrey A. Bluestone Qizhi Tang Qizhi Tang Jonathan H. Esensten
author_sort	Joanna Balcerek
title	Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
title_short	Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
title_full	Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
title_fullStr	Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
title_full_unstemmed	Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
title_sort	polyclonal regulatory t cell manufacturing under cgmp: a decade of experience
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4fbc3387d354494ba9daa3d9eab90fba
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Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience

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