Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress
Nivolumab, formulated in the medicine Opdivo<sup>®</sup> (10 mg/mL), is a therapeutic monoclonal antibody (mAb) used in the treatment of different types of cancer. Currently, there is insufficient knowledge about the behaviour of this protein with regards to the risk associated with its...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/4/692 |
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| author | Anabel Torrente-López Jesús Hermosilla Antonio Salmerón-García José Cabeza Natalia Navas |
| author_facet | Anabel Torrente-López Jesús Hermosilla Antonio Salmerón-García José Cabeza Natalia Navas |
| author_sort | Anabel Torrente-López |
| collection | DOAJ |
| description | Nivolumab, formulated in the medicine Opdivo<sup>®</sup> (10 mg/mL), is a therapeutic monoclonal antibody (mAb) used in the treatment of different types of cancer. Currently, there is insufficient knowledge about the behaviour of this protein with regards to the risk associated with its routine handling or unintentional mishandling, or when subjected to stress conditions in hospitals. These conditions can be simulated in forced degradation studies, which provide an in-depth understanding of the biophysical and biochemical properties of mAbs. In this study, we carried out a physicochemical and functional characterisation of nivolumab, which was subjected to various stress conditions: heat, freeze/thaw cycles, agitation, light exposure and high hypertonic solution. We used a wide range of analytical techniques: Far-UV CD, IT-FS, DLS, SE/UHPLC(UV)-[Native]MS, and ELISA. The results show that exposure to light was the stress test with the greatest impact on the samples, revelling the formation of non-natural dimers and a different isoform profile. In addition, nivolumab (Opdivo<sup>®</sup>) demonstrated stability up to 60 °C (1 h). As regards functionality all the nivolumab (Opdivo<sup>®</sup>) stressed samples were found to be stable except for those subjected to light and agitation, and to a lesser extent, those subjected to FTC 5 and NaCl stresses. |
| first_indexed | 2024-03-09T13:09:58Z |
| format | Article |
| id | doaj.art-c1d95b49addc42dba14c179d61891d30 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T13:09:58Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c1d95b49addc42dba14c179d61891d302023-11-30T21:43:29ZengMDPI AGPharmaceutics1999-49232022-03-0114469210.3390/pharmaceutics14040692Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and StressAnabel Torrente-López0Jesús Hermosilla1Antonio Salmerón-García2José Cabeza3Natalia Navas4Department of Analytical Chemistry, Science Faculty, Biohealth Research Institute (ibs.GRANADA), University of Granada, E-18071 Granada, SpainDepartment of Analytical Chemistry, Science Faculty, Biohealth Research Institute (ibs.GRANADA), University of Granada, E-18071 Granada, SpainDepartment of Clinical Pharmacy, Biohealth Research Institute (ibs.GRANADA), San Cecilio University Hospital, E-18012 Granada, SpainDepartment of Clinical Pharmacy, Biohealth Research Institute (ibs.GRANADA), San Cecilio University Hospital, E-18012 Granada, SpainDepartment of Analytical Chemistry, Science Faculty, Biohealth Research Institute (ibs.GRANADA), University of Granada, E-18071 Granada, SpainNivolumab, formulated in the medicine Opdivo<sup>®</sup> (10 mg/mL), is a therapeutic monoclonal antibody (mAb) used in the treatment of different types of cancer. Currently, there is insufficient knowledge about the behaviour of this protein with regards to the risk associated with its routine handling or unintentional mishandling, or when subjected to stress conditions in hospitals. These conditions can be simulated in forced degradation studies, which provide an in-depth understanding of the biophysical and biochemical properties of mAbs. In this study, we carried out a physicochemical and functional characterisation of nivolumab, which was subjected to various stress conditions: heat, freeze/thaw cycles, agitation, light exposure and high hypertonic solution. We used a wide range of analytical techniques: Far-UV CD, IT-FS, DLS, SE/UHPLC(UV)-[Native]MS, and ELISA. The results show that exposure to light was the stress test with the greatest impact on the samples, revelling the formation of non-natural dimers and a different isoform profile. In addition, nivolumab (Opdivo<sup>®</sup>) demonstrated stability up to 60 °C (1 h). As regards functionality all the nivolumab (Opdivo<sup>®</sup>) stressed samples were found to be stable except for those subjected to light and agitation, and to a lesser extent, those subjected to FTC 5 and NaCl stresses.https://www.mdpi.com/1999-4923/14/4/692nivolumabcomprehensive analytical characterisationforced degradationUHPLC-MSisoform profile |
| spellingShingle | Anabel Torrente-López Jesús Hermosilla Antonio Salmerón-García José Cabeza Natalia Navas Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress Pharmaceutics nivolumab comprehensive analytical characterisation forced degradation UHPLC-MS isoform profile |
| title | Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress |
| title_full | Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress |
| title_fullStr | Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress |
| title_full_unstemmed | Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress |
| title_short | Comprehensive Analysis of Nivolumab, A Therapeutic Anti-Pd-1 Monoclonal Antibody: Impact of Handling and Stress |
| title_sort | comprehensive analysis of nivolumab a therapeutic anti pd 1 monoclonal antibody impact of handling and stress |
| topic | nivolumab comprehensive analytical characterisation forced degradation UHPLC-MS isoform profile |
| url | https://www.mdpi.com/1999-4923/14/4/692 |
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