Article
Biochemical Research Methods
Thomas Bouvarel, Bastiaan L. Duivelshof, Julien Camperi, Tilman Schlothauer, Alexander Knaupp, Cinzia Stella, Davy Guillarme
Summary: In this study, a new strategy to improve the performance of affinity chromatography with monoclonal antibody (mAb) species is proposed. The strategy involves the use of pH-gradient programs that incorporate multi-isocratic and negative gradient segments, which greatly improve separation and selectivity.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Review
Biochemistry & Molecular Biology
Maxime Fieux, Sandra Le Quellec, Sophie Battier, Andre Coste, Bruno Louis, Caroline Giroudon, Mikail Nourredine, Emilie Bequignon
Summary: FcRn has been shown to efficiently transport biologics across the nasal epithelial barrier in multiple studies reviewed. Limited studies have evaluated the potential toxicity of intranasal delivery of biologics, but they all indicate its safety. Further research is needed to fully understand the pharmacokinetic and pharmacodynamic properties of biologics after intranasal delivery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gilles Thibault, Gilles Paintaud, Hsueh Cheng Sung, Laurie Lajoie, Edouard Louis, Celine Desvignes, Herve Watier, Valerie Gouilleux-Gruart, David Ternant
Summary: Fc gamma RIIA/CD32A is expressed on platelets and some endothelial cells, playing a role in binding IgG antibodies, which may contribute to their elimination. Platelet Fc gamma RIIA's affinity for different IgG subclasses influences the clearance of antibodies like infliximab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Justin Thomas, Molly A. Torok, Kriti Agrawal, Timothy Pfau, Trang T. Vu, Justin Lyberger, Hsiaochi Chang, Alyssa Marie M. Castillo, Min Chen, Bryan Remaily, Kyeongmin Kim, Zhiliang Xie, Mary E. Dillhoff, Samuel K. Kulp, Gregory K. Behbehani, Zobeida Cruz-Monserrate, Latha P. Ganesan, Dwight H. Owen, Mitch A. Phelps, Christopher C. Coss, Thomas A. Mace
Summary: The neonatal Fc receptor (FcRn) is responsible for recycling antibodies and albumin in the body. However, little is known about its expression in circulating immune cells. In this study, FcRn expression was found to be elevated in immune cells of pancreatic ductal adenocarcinoma (PDAC) patients and mice with PDAC. These findings may contribute to understanding the mechanisms behind poor efficacy of antibody immunotherapies in PDAC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Timothy Qi, Yanguang Cao
Summary: This review examines the biological and thermodynamic properties of FcRn and recent advancements in the field, including Fab determinants of FcRn affinity, transgenic preclinical models, and FcRn targeting for immune-complex clearance. It also evaluates the potential of therapeutic antibodies for SARS-CoV-2 to saturate FcRn-mediated recycling. The importance of endosomal transit parameters in the quantitative relationship between in vivo IgG persistence and in vitro FcRn binding is emphasized through modeling and simulation studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Hanine Rafidi, Sharmila Rajan, Konnie Urban, Whitney Shatz-Binder, Keliana Hui, Gregory Z. Ferl, Amrita V. Kamath, C. Andrew Boswell
Summary: Advances in antibody engineering have provided new opportunities for biologic therapies, and understanding the impact of structural factors on antibody distribution properties is crucial. This study evaluated the effect of antibody size on systemic pharmacokinetics and tissue distribution. The results showed that circulating antibody had the greatest contribution to total uptake in early time points and highly vascularized tissues. Tissue interstitial pharmacokinetics largely mirrored serum exposure profiles, except for non-FcRn-binding molecules which showed changing interstitial:serum ratios over time. Additionally, the study measured concentration-time profiles of intact and catabolized molecules, revealing that IgG-HAHQ had the highest catabolism levels.
Article
Biochemical Research Methods
Wenhong Fan, Xiang Li, Zhen Long, Dening Pei, Xinchang Shi, Guangyu Wang, Ying Guo, Tao Bo, Yong Zhou, Tong Chen
Summary: Fc-fusion proteins combine the pharmacological properties of biological ligands with the functions of immunoglobulins. Analytical characterization of fusion proteins is more complex than monoclonal antibodies, requiring specific methods. The integration of UHPLC-MS and icIEF provided an innovative strategy for characterizing complex fusion proteins.
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
(2023)
Article
Chemistry, Analytical
Cuiyan Cao, Long Yu, Xiuli Zhang, Xuefang Dong, Jingli Yuan, Xinmiao Liang
Summary: The calibration strategy using a library of glycopeptide standards significantly improved the accuracy and precision of Fc-glycosylation analysis of mAbs, especially when coupled with HILIC separation. Transferability of the calibrated quantitation across different instruments and laboratories was also enhanced, indicating its utility for Fc-glycosylation analysis of IgG1-type mAbs with multiple glycosylation sites.
ANALYTICA CHIMICA ACTA
(2021)
Article
Biochemistry & Molecular Biology
Christophe Macri, Huw Morgan, Jose A. Villadangos, Justine D. Mintern
Summary: Dendritic cells (DCs) express receptors to sense pathogens and communicate with other immune cells. Fc receptors (FcRs) play a crucial role in DC immunity, affecting antigen uptake, presentation, DC maturation, and polarization of T cell responses.
MOLECULAR IMMUNOLOGY
(2021)
Article
Chemistry, Analytical
Gang Wu, Chuanfei Yu, Wenbo Wang, Jialiang Du, Zhihao Fu, Gangling Xu, Meng Li, Lan Wang
Summary: Imaged capillary isoelectric focusing (icIEF) and ion exchange chromatography (IEX) are routinely used for charge variant analysis of therapeutic monoclonal antibodies (mAbs). In this study, icIEF-MS and strong cation exchange (SCX)-MS were compared, and it was found that icIEF-MS outperformed SCX-MS in terms of sensitivity, carryover effect, protein identification, and separation resolution.
ANALYTICAL CHEMISTRY
(2023)
Article
Dermatology
Dario Didona, Giovanni Paolino, Giovanni Di Zenzo, Biagio Didona, Riccardo Pampena, Matteo Riccardo Di Nicola, Santo Raffaele Mercuri
Summary: Pemphigus vulgaris (PV) is an autoimmune blistering disease. Glucocorticoids have improved the prognosis of patients with PV, but long-term use can lead to adverse effects. Rituximab and other antibody therapies have shown promising results in the treatment of PV.
DERMATOLOGY PRACTICAL & CONCEPTUAL
(2022)
Article
Chemistry, Analytical
Victoria C. Cotham, Anita P. Liu, Shunhai Wang, Ning Li
Summary: Affinity chromatography coupled with native mass spectrometry is a powerful tool for studying therapeutic monoclonal antibodies. However, its routine application has been limited due to complex experimental set up. This study introduces a generic platform, enabling simplified experimental set up and facile swapping of affinity separation modes, and demonstrates successful online coupling of three affinity chromatography methods with native mass spectrometry.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Review
Immunology
Kristin Hovden Aaen, Aina Karen Anthi, Inger Sandlie, Jeannette Nilsen, Simone Mester, Jan Terje Andersen
Summary: FcRn is a versatile receptor that rescues IgG and albumin from degradation and facilitates their transport across cells via a pH-dependent mechanism. It plays a crucial role in immune surveillance, antigen presentation, and protection against infections by regulating ligand transport and immune complex processing. This biology can be utilized in the development of biologics and subunit vaccines for non-invasive delivery.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chandra B. Prabaharan, Sabeena Giri, Kevin J. H. Allen, Katrina E. M. Bato, Therese R. Mercado, Mackenzie E. Malo, Jorge L. C. Carvalho, Ekaterina Dadachova, Maruti Uppalapati
Summary: Novel therapeutic approaches, such as targeted radionuclide therapy (TRT) and radioimmunotherapy (RIT), are promising for the treatment of osteosarcoma. Researchers have developed an improved version of a human antibody called IF3 & delta;, which effectively inhibits tumor growth. The study also suggests that both IF3 and IF3 & delta; have potential for RIT of osteosarcoma.
Article
Pharmacology & Pharmacy
Valegh Faid, Yann Leblanc, Marie Berger, Alexander Seifert, Nicolas Bihoreau, Guillaume Chevreux
Summary: Research shows that the C-terminal lysine clipping of monoclonal antibodies does not have a significant impact on their ability to bind human Fc receptors, resulting in comparable biological properties.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Christophe Passot, Rebecca Sberro-Soussan, Dominique Bertrand, Sophie Caillard, Betoul Schvartz, Camille Domenger, Cecile Contin-Bordes, Gilles Paintaud, Jean-Michel Halimi, David Ternant, Philippe Gatault
Summary: This study demonstrated the feasibility of therapeutic drug monitoring of eculizumab in atypical haemolytic-uraemic syndrome patients. Through pharmacokinetic monitoring, it was found that extending the interval between infusions could effectively increase drug concentrations.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Olivier Le Tilly, Nicolas Azzopardi, Claire Bonneau, Celine Desvignes, Florence Oberkampf, Monia Ezzalfani, David Ternant, Isabelle Turbiez, Maya Gutierrez, Gilles Paintaud
Summary: Intravenous administration of monoclonal antibodies results in low concentrations in the central nervous system, posing challenges in neuro-oncology, particularly in cases of leptomeningeal carcinomatosis of HER2-overexpressing breast cancer. This study describes the fate of trastuzumab after intrathecal administration, revealing significant fluctuations in cerebrospinal fluid concentration and rapid transfer to serum. Transfer of trastuzumab from serum to cerebrospinal fluid is limited, and intrathecal administration is associated with rapid transfer to serum, with no correlation to survival without neurological relapse.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemical Research Methods
Celine Desvignes, David Ternant, Thierry Lecomte, Astrid Lievre, Marc Ohresser, Romain Chautard, William Raoul, Gilles Paintaud
Summary: An ELISA assay measuring ramucirumab serum concentrations was developed and validated, suitable for pharmacokinetic studies of ramucirumab with good sensitivity, accuracy, reproducibility.
Meeting Abstract
Oncology
S. Lobet, G. Paintaud, N. Azzopardi, C. Passot, M. Caulet, R. Chautard, C. Vignault-Desvignes, O. Capitain, D. Tougeron, M. Boisdron-Celle, D. Ternant, T. Lecomte
ANNALS OF ONCOLOGY
(2021)
Meeting Abstract
Rheumatology
M. A. Sparfel, S. Derolez, J. Law-Wan, N. Azzopardi, P. Goupille, D. Mulleman, T. Bejan-Angoulvant
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Medicine, Research & Experimental
Romain Chautard, Laetitia Corset, Sajida Ibrahim, Celine Desvignes, Gilles Paintaud, Nadine Baroukh, Maxime Gueguinou, Thierry Lecomte, William Raoul
Summary: The study found significant effects of cetuximab and panitumumab exposure on miR expression in colorectal cancer cells, with some miR interacting with downstream elements of the EGFR pathway. 5 miRs rarely described before were identified as potential actors of anti-EGFR monoclonal antibody resistance, and miR-139-5p and miR-145-5p were detected in the serum of patients with metastatic CRC.
BIOMARKERS IN MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Nicolas Azzopardi, Helene Longuet, David Ternant, Gilles Thibault, Valerie Gouilleux-Gruart, Yvon Lebranchu, Matthias Buchler, Philippe Gatault, Gilles Paintaud
Summary: The study developed a model describing the pharmacokinetics and pharmacodynamics of rabbit antithymocyte globulins in kidney transplant patients. Results indicated that the dosing of rATG is influenced by patient age and body surface area, which could be used to design clinical trials testing dose individualization based on patient characteristics.
CLINICAL PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
A. Petitcollin, N. Azzopardi, J. Y. Pierga, D. Ternant, I Navarro-Teulon, C. Desvignes, M. A. Mouret-Reynier, B. Coudert, G. Paintaud
Summary: The study aimed to describe the sources of interindividual variability of bevacizumab and trastuzumab pharmacokinetics and to study the relationship between exposure and early clinical response and specific adverse events in early-stage breast cancer patients. The results showed that tumor uptake influenced the pharmacokinetics of these antibodies, and in this population, elimination half-lives of these therapeutic monoclonal antibodies may be shorter than previously reported in more advanced disease.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Rheumatology
Johan Law-Wan, Marc-Antoine Sparfel, Sophie Derolez, Nicolas Azzopardi, Philippe Goupille, Jacqueline Detert, Denis Mulleman, Theodora Bejan-Angoulvant
Summary: In rheumatoid arthritis (RA), patients who are more responsive to TNFi are those who are non-obese, have a longer disease duration, and have a higher initial disease activity. Results from analyzing individual data of 11,617 patients from 29 RCTs highlight the importance of these patient characteristics in predicting responsiveness to TNFi therapy.
Letter
Infectious Diseases
Xavier de Lamballerie, Guillaume Martin-Blondel, Axelle Dupont, Jacques Izopet, France Mentre, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Alienor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Denis Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stephanie N. Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Vincent Levy
JOURNAL OF INFECTION
(2023)
Article
Pharmacology & Pharmacy
Sarah Lobet, Gilles Paintaud, Nicolas Azzopardi, Christophe Passot, Morgane Caulet, Romain Chautard, Celine Desvignes, Olivier Capitain, David Tougeron, Thierry Lecomte, David Ternant
Summary: This study investigated the relationship between cetuximab concentrations, target kinetics, and progression-free survival (PFS) using target-mediated drug disposition (TMDD) modeling. The results described the complex relationship between the pharmacokinetics of cetuximab and PFS in metastatic colorectal cancer (mCRC) patients using a joint PK-time-to-progression model.
CLINICAL PHARMACOKINETICS
(2023)
Meeting Abstract
Pharmacology & Pharmacy
O. Le Tilly, N. Azzopardi, C. Bonneau, C. Desvignes, D. Ternant, I. Turbiez, M. Gutierrez, G. Paintaud
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
I. Ma, D. Angoulvant, N. Azzopardi, D. Ternant, F. Ivanes, G. Paintaud, T. Bejan Angoulvant
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2021)
Article
Oncology
David Tougeron, Sheik Emambux, Laure Favot, Thierry Lecomte, Ewa Wierzbicka-Hainaut, Mahtab Samimi, Eric Frouin, Nicolas Azzopardi, Jocelyn Chevrier, Laura Serres, Julie Godet, Pierre Levillain, Gilles Paintaud, Aurelie Ferru, Laetitia Rouleau, Adriana Delwail, Christine Silvain, Jean-Pierre Tasu, Franck Morel, Stephanie Ragot, Jean-Claude Lecron
Article
Oncology
Frederic Dumont, Christophe Passot, Jean-Luc Raoul, Vahan Kepenekian, Benedicte Lelievre, Michelle Boisdron-Celle, Sandrine Hiret, Helene Senellart, Francois Pein, Audrey Blanc-Lapierre, Judith Raimbourg, Emilie Thibaudeau, Olivier Glehen
EUROPEAN JOURNAL OF CANCER
(2020)