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Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation

Cytokine-induced killer (CIK) cells are advanced therapy medicinal products, so their production and freezing process has to be validated before their clinical use, to verify their stability as a drug formulation according to the good manufacturing practice (GMP) guidelines. We designed a stability...

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Autores principales: Mareschi, Katia, Adamini, Aloe, Castiglia, Sara, Rustichelli, Deborah, Castello, Laura, Mandese, Alessandra, Leone, Marco, Pinnetta, Giuseppe, Mesiano, Giulia, Ferrero, Ivana, Fagioli, Franca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281026/
https://www.ncbi.nlm.nih.gov/pubmed/32408620
http://dx.doi.org/10.3390/ph13050093
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author Mareschi, Katia
Adamini, Aloe
Castiglia, Sara
Rustichelli, Deborah
Castello, Laura
Mandese, Alessandra
Leone, Marco
Pinnetta, Giuseppe
Mesiano, Giulia
Ferrero, Ivana
Fagioli, Franca
author_facet Mareschi, Katia
Adamini, Aloe
Castiglia, Sara
Rustichelli, Deborah
Castello, Laura
Mandese, Alessandra
Leone, Marco
Pinnetta, Giuseppe
Mesiano, Giulia
Ferrero, Ivana
Fagioli, Franca
author_sort Mareschi, Katia
collection PubMed
description Cytokine-induced killer (CIK) cells are advanced therapy medicinal products, so their production and freezing process has to be validated before their clinical use, to verify their stability as a drug formulation according to the good manufacturing practice (GMP) guidelines. We designed a stability program for our GMP-manufactured CIK cells, evaluating the viability, identity and potency of cryopreserved CIK cells at varying time periods from freezing, and compared them with fresh CIK cells. We evaluated the effects of the cryopreservation method, transportation, and the length of time of different process phases (pre-freezing, freezing and post-thawing) on the stability of CIK cells. This included a worst case for each stage. The expanded CIK cells were viable for up to 30 min from the addition of the freezing solution, when transported on dry ice within 48 h once frozen, within 60 min from thawing and from 12 months of freezing while preserving their cytotoxic effects. The reference samples, cryopreserved simultaneously in tubes and following the same method, were considered representative of the batch and useful in the case of further analysis. Data obtained from this drug stability program can inform the accurate use of CIK cells in clinical settings.
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spelling pubmed-72810262020-06-15 Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation Mareschi, Katia Adamini, Aloe Castiglia, Sara Rustichelli, Deborah Castello, Laura Mandese, Alessandra Leone, Marco Pinnetta, Giuseppe Mesiano, Giulia Ferrero, Ivana Fagioli, Franca Pharmaceuticals (Basel) Article Cytokine-induced killer (CIK) cells are advanced therapy medicinal products, so their production and freezing process has to be validated before their clinical use, to verify their stability as a drug formulation according to the good manufacturing practice (GMP) guidelines. We designed a stability program for our GMP-manufactured CIK cells, evaluating the viability, identity and potency of cryopreserved CIK cells at varying time periods from freezing, and compared them with fresh CIK cells. We evaluated the effects of the cryopreservation method, transportation, and the length of time of different process phases (pre-freezing, freezing and post-thawing) on the stability of CIK cells. This included a worst case for each stage. The expanded CIK cells were viable for up to 30 min from the addition of the freezing solution, when transported on dry ice within 48 h once frozen, within 60 min from thawing and from 12 months of freezing while preserving their cytotoxic effects. The reference samples, cryopreserved simultaneously in tubes and following the same method, were considered representative of the batch and useful in the case of further analysis. Data obtained from this drug stability program can inform the accurate use of CIK cells in clinical settings. MDPI 2020-05-12 /pmc/articles/PMC7281026/ /pubmed/32408620 http://dx.doi.org/10.3390/ph13050093 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mareschi, Katia
Adamini, Aloe
Castiglia, Sara
Rustichelli, Deborah
Castello, Laura
Mandese, Alessandra
Leone, Marco
Pinnetta, Giuseppe
Mesiano, Giulia
Ferrero, Ivana
Fagioli, Franca
Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation
title Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation
title_full Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation
title_fullStr Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation
title_full_unstemmed Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation
title_short Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation
title_sort cytokine-induced killer (cik) cells, in vitro expanded under good manufacturing process (gmp) conditions, remain stable over time after cryopreservation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281026/
https://www.ncbi.nlm.nih.gov/pubmed/32408620
http://dx.doi.org/10.3390/ph13050093
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