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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/13/5/93 |
| _version_ | 1797568143849160704 |
|---|---|
| author | Katia Mareschi Aloe Adamini Sara Castiglia Deborah Rustichelli Laura Castello Alessandra Mandese Marco Leone Giuseppe Pinnetta Giulia Mesiano Ivana Ferrero Franca Fagioli |
| author_facet | Katia Mareschi Aloe Adamini Sara Castiglia Deborah Rustichelli Laura Castello Alessandra Mandese Marco Leone Giuseppe Pinnetta Giulia Mesiano Ivana Ferrero Franca Fagioli |
| author_sort | Katia Mareschi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:52:17Z |
| format | Article |
| id | doaj.art-1cd2b7c216af419babe79916e49437ff |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T19:52:17Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-1cd2b7c216af419babe79916e49437ff2023-11-20T00:12:33ZengMDPI AGPharmaceuticals1424-82472020-05-011359310.3390/ph13050093Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after CryopreservationKatia Mareschi0Aloe Adamini1Sara Castiglia2Deborah Rustichelli3Laura Castello4Alessandra Mandese5Marco Leone6Giuseppe Pinnetta7Giulia Mesiano8Ivana Ferrero9Franca Fagioli10Department of Public Health and Paediatrics, The University of Turin, piazza Polonia 94. 10126 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyDepartment of Public Health and Paediatrics, The University of Turin, piazza Polonia 94. 10126 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyDepartment of Oncology, University of Turin, 10060 Torino, ItalyStem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin; 10126 Torino, ItalyDepartment of Public Health and Paediatrics, The University of Turin, piazza Polonia 94. 10126 Torino, ItalyCytokine-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.https://www.mdpi.com/1424-8247/13/5/93advanced therapy medicinal product (ATMP)good manufacturing practice (GMP)cytokine-induced killer (CIK) cellscryopreservationdrug formulationstability program |
| spellingShingle | Katia Mareschi Aloe Adamini Sara Castiglia Deborah Rustichelli Laura Castello Alessandra Mandese Marco Leone Giuseppe Pinnetta Giulia Mesiano Ivana Ferrero Franca Fagioli Cytokine-Induced Killer (CIK) Cells, In Vitro Expanded under Good Manufacturing Process (GMP) Conditions, Remain Stable over Time after Cryopreservation Pharmaceuticals advanced therapy medicinal product (ATMP) good manufacturing practice (GMP) cytokine-induced killer (CIK) cells cryopreservation drug formulation stability program |
| 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 | advanced therapy medicinal product (ATMP) good manufacturing practice (GMP) cytokine-induced killer (CIK) cells cryopreservation drug formulation stability program |
| url | https://www.mdpi.com/1424-8247/13/5/93 |
| work_keys_str_mv | AT katiamareschi cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT aloeadamini cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT saracastiglia cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT deborahrustichelli cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT lauracastello cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT alessandramandese cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT marcoleone cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT giuseppepinnetta cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT giuliamesiano cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT ivanaferrero cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation AT francafagioli cytokineinducedkillercikcellsinvitroexpandedundergoodmanufacturingprocessgmpconditionsremainstableovertimeaftercryopreservation |