Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressurized intraperitoneal aerosol chemotherapy.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_6E436E5918F9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Assessment of chemical stability of monoclonal antibody and antibody drug conjugate administered by pressurized intraperitoneal aerosol chemotherapy.
Journal
Journal of pharmaceutical and biomedical analysis
Author(s)
D'Atri V., Galy G., Buff M., Imiołek M., Hübner M., Undurraga M., Labidi-Galy S.I., Guillarme D., Carrez L.
ISSN
1873-264X (Electronic)
ISSN-L
0731-7085
Publication state
Published
Issued date
15/12/2024
Peer-reviewed
Oui
Volume
251
Pages
116410
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new therapeutic approach for patients with peritoneal cancer. So far, most published studies investigated the administration of established cytostatic agents through PIPAC. This study aimed to evaluate the effect of PIPAC on two breakthrough anti-cancer agents, specifically anti-PD1 pembrolizumab, and anti-HER2 antibody-drug conjugate (ADC) - trastuzumab-deruxtecan. We conducted systematic analyses on samples of pembrolizumab and trastuzumab-deruxtecan at clinically relevant concentrations before and after PIPAC administration using an experimental setup of a hermetic container system, mimicking the abdominal cavity and using identical features as in clinical use. We utilized a range of chromatographic and spectroscopic techniques to explore potential alterations in the primary, secondary, and tertiary structures of the drugs, focusing on post-translational modifications resulting from the aerosolization. Our findings indicate that PIPAC did not compromise the integrity of tested biopharmaceuticals. The size variants of both drugs, assessed by size exclusion chromatography (SEC), remained unchanged. Reversed-phase liquid chromatography (RPLC) and hydrophobic interaction chromatography (HIC) revealed no significant differences in hydrophobicity variants, the average drug-to-antibody ratio (DAR), or DAR distribution before and after PIPAC treatment. Circular dichroism (CD) spectroscopy confirmed that the secondary and tertiary structures were preserved. While pembrolizumab showed no change in charge variants post-PIPAC, trastuzumab-deruxtecan exhibited a non-negligible change in the quantity of charge variants on the monoclonal antibody itself, while the payload remained unchanged. This shift could possibly be related to the metallic composition of the CapnoPen® device (made of nickel and chromium) used in PIPAC and for these experiments. Together, our results suggest that PIPAC does not alter the structure of pembrolizumab and trastuzumab-deruxtecan, paving the way for future clinical trials.
Keywords
Aerosols/chemistry, Trastuzumab/chemistry, Immunoconjugates/chemistry, Immunoconjugates/analysis, Immunoconjugates/administration & dosage, Drug Stability, Antibodies, Monoclonal, Humanized/chemistry, Antibodies, Monoclonal, Humanized/analysis, Antibodies, Monoclonal, Humanized/administration & dosage, Humans, Peritoneal Neoplasms/drug therapy, Antibodies, Monoclonal/chemistry, Antibodies, Monoclonal/administration & dosage, Receptor, ErbB-2/antagonists & inhibitors, Pressure, PIPAC, Pembrolizumab Keytruda®, Pressurized intra-peritoneal aerosol chemotherapy, Stability, Trastuzumab-deruxtecan enhertu®, antibody drug conjugate, drug to antibody ratio
Pubmed
Web of science
Open Access
Yes
Create date
30/08/2024 9:45
Last modification date
24/09/2024 6:25
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