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
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
Immunology
Noemie Corcos, Slobodan Culina, Claire Deligne, Cassandra Lavaud, Sylvaine You, Roberto Mallone
Summary: While neonatal oral PPI-Fc vaccination did not prevent diabetes development in PPI T-cell receptor-transgenic G9C8.NOD mice, it efficiently transferred through the intestinal epithelium in an Fc- and FcRn-dependent manner, reaching antigen presenting cells in the spleen and thymus. In polyclonal Ins2(-/-).NOD mice that spontaneously develop accelerated diabetes, neonatal oral PPI-Fc vaccination showed promise by delaying diabetes onset, although further improvements in the current PPI-Fc formulation/regimen are needed for diabetes prevention.
FRONTIERS IN IMMUNOLOGY
(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
Immunology
Celine Monnet, Emilie Jacque, Christophe de Romeuf, Alexandre Fontayne, Toufik Abache, Nathalie Fournier, Gilles Dupont, Delphine Derache, Anais Engrand, Aurelie Bauduin, Aurelie Terrier, Alexander Seifert, Cecile Beghin, Alain Longue, Nicholas Masiello, Laetitia Danino, Michel Nogre, Anais Raia, Frederic Dhainaut, Louis Fauconnier, Dieudonnee Togbe, Carmen Reitinger, Falk Nimmerjahn, Wil Stevens, Sami Chtourou, Philippe Mondon
Summary: Recently developed novel molecules targeting FcRn and/or Fc gamma R receptors show promising potential in treating IgG-dependent autoimmune pathologies. One of these molecules, LFBD192, engineered for optimal binding to both human and mouse Fc receptors, demonstrates superior efficacy compared to existing treatments like IVIg and FcRn blockers, and has been validated in vitro and in mouse models of autoimmune disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Miho Nagayasu, Kazuhisa Ozeki
Summary: The study aimed to develop a useful antibody PK evaluation tool by combining cassette-dosing and microsampling in mice and monkeys to reduce the number of animals used. Results showed that this new method can significantly reduce the number of animals while ensuring similar PK parameters.
PHARMACEUTICAL RESEARCH
(2021)
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
Cell Biology
Eileen Dahlke, Yaman Anan, Lea Maximiliane Klie, Ariane Elisabeth Hartkopf, Franziska Theilig
Summary: The neonatal Fc receptor (FcRn) is highly expressed in the renal proximal tubule and plays a crucial role in the reclamation of albumin by cellular transcytosis. The interaction between megalin and FcRn in the endosomal compartment was detected, which increased when endocytosis was induced. Megalin orchestrates the endocytosis and intracellular trafficking of FcRn as an early event in transcytosis.
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Takahiro Mikami, Yasuko Tsukazaki, Yasuharu Nakanishi, Norie Murayama, Shinichi Ikushiro, Hideshi Tsusaki, Hiroshi Yamazaki
Summary: In cynomolgus and rhesus macaques, genetic variants in UGT1A1/6/9 genes were identified, including unique variants specific to each species. The study suggests that these variants, such as UGT1A1G69R, may affect the glucuronidation of drugs mediated by UGT1A1 in these macaque species.
Review
Clinical Neurology
Vinaya Bhandari, Vera Bril
Summary: Myasthenia gravis (MG) is an autoimmune disorder characterized by antibodies attacking proteins in the neuromuscular junction. Current therapies for MG have significant side effects. Recent research on FcRn receptors suggests that blocking them can enhance the degradation of IgG, similar to plasma exchange but with fewer safety concerns. Several FcRn therapeutic agents are being tested in clinical trials for MG treatment.
FRONTIERS IN NEUROLOGY
(2023)
Article
Veterinary Sciences
Shijing Sun, Hui Jiang, Qiaoling Li, Yufu Liu, Qiang Gao, Wei Liu, Yuming Qin, Yu Feng, Xiaowei Peng, Guanlong Xu, Qingchun Shen, Xuezheng Fan, Jiabo Ding, Liangquan Zhu
Summary: The study evaluated the safety of the S2 vaccine strain on primates using cynomolgus monkeys as animal models. Results indicated that the S2 vaccine was safe for cynomolgus monkeys, with transcriptome analysis revealing differentially expressed genes involved in various biological processes. This study provides a genetic basis for understanding host response following vaccination with the S2 vaccine.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Guglielmo Vesco, Marta Lualdi, Mauro Fasano, Luca Nardo, Tiziana Alberio
Summary: The study provides direct evidence of binding interaction between FcRn and fibrinogen at acidic pH, suggesting a protective mechanism for fibrinogen from degradation and regulation of its plasma levels. This interaction may also impact the levels of other FcRn binding partners, including clinically relevant plasma proteins.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Immunology
Ria Lassauniere, Caroline T. Tiemessen
Summary: Research on the Fc receptors for Immunoglobulin G suggests their crucial role in the immune response, particularly in HIV-1 vaccine efficacy trials. Host genetic correlates within the low affinity Fc gamma-receptor locus have been identified in HIV-1 efficacy trials, shedding light on the potential contribution of Fc gamma R variability in modulating different HIV-1 vaccine efficacy outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Xinfang Xie, Jingyi Li, Pan Liu, Manliu Wang, Li Gao, Feng Wan, Jicheng Lv, Hong Zhang, Jing Jin
Summary: We constructed a chimeric fusion of IgA protease with Fc and demonstrated its long-lasting efficacy as a promising targeted therapy for IgA nephropathy in mouse models.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Immunology
Yuko Nakajima-Kato, Masato Komai, Tadashi Yoshida, Akiko Kanai
Summary: In this study, a Fc-modified anti-Haptoglobin monoclonal antibody was developed and found to have comparable efficacy to IVIG but at considerably lower doses. In vitro experiments demonstrated its binding activity to Fc gamma receptors and inhibitory activity in the ADCC reaction. Furthermore, a cynomolgus monkey ITP model was successfully established, and the antibody showed therapeutic effects with only a single dose. This Fc-modified anti-Haptoglobin monoclonal antibody could be a valuable alternative to IVIG for ITP treatment.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Hiroshi Yamazaki
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Shotaro Uehara, Takashi Inoue, Shu Kawamura, Norie Murayama, Miyu Nishikawa, Shinichi Ikushiro, Erika Sasaki, Hiroshi Yamazaki
BIOCHEMICAL PHARMACOLOGY
(2020)
Review
Pharmacology & Pharmacy
Shotaro Uehara, Yasuhiro Uno, Hiroshi Yamazaki
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Pharmacology & Pharmacy
Kayoko Ohura, Yoshiyuki Igawa, Maori Tanaka, Kana Matsumoto, Akiko Kasahara, Naoya Wada, Kazuishi Kubota, Yasuhiro Uno, Teruko Imai
DRUG METABOLISM AND DISPOSITION
(2020)
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Hiroshi Yamazaki
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Pharmacology & Pharmacy
Shotaro Uehara, Yasuhiro Uno, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Pharmacology & Pharmacy
Makiko Shimizu, Yasuhiro Uno, Masahiro Utoh, Hiroshi Yamazaki
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Hiroshi Yamazaki
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Pharmacology & Pharmacy
Shotaro Uehara, Yasuhiro Uno, Hiroshi Yamazaki
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Pharmacology & Pharmacy
Shotaro Uehara, Yasuhiro Uno, Hiroshi Yamazaki
DRUG METABOLISM AND PHARMACOKINETICS
(2020)
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Shotaro Uehara, Norie Murayama, Makiko Shimizu, Hiroshi Yamazaki
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Takahiro Mikami, Yasuko Tsukazaki, Yasuharu Nakanishi, Norie Murayama, Shinichi Ikushiro, Hideshi Tsusaki, Hiroshi Yamazaki
Summary: In cynomolgus and rhesus macaques, genetic variants in UGT1A1/6/9 genes were identified, including unique variants specific to each species. The study suggests that these variants, such as UGT1A1G69R, may affect the glucuronidation of drugs mediated by UGT1A1 in these macaque species.
Article
Pharmacology & Pharmacy
Yasuhiro Uno, Shotaro Uehara, Norie Murayama, Hiroshi Yamazaki
Summary: Genetic variants in AOX1 were identified and allele frequencies were assessed in cynomolgus and rhesus macaques. The study found that AOX1 is polymorphic in these non-human primate species, suggesting potential impacts on drug metabolism that require further investigation.
Article
Pharmacology & Pharmacy
Yurie Okawa, Sakae Kohara, Asako Uchiyama, Hiroshi Yamazaki, Yasuhiro Uno
Summary: The biodistribution profile of cell-based therapy products in animal models is crucial for evaluating their safety and efficacy, with qPCR being a useful method for detecting and quantifying xenogeneic cell-derived DNA. The use of the DUF1220 gene for analysis showed promising results in differentiating human genome from mouse and cynomolgus monkey genomes, providing potential for future biodistribution studies.
DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Correction
Pharmacology & Pharmacy
S. Uehara, Y. Uno, T. Inoue, M. Kawano, M. Shimizu, A. Toda, M. Utoh, E. Sasaki, H. Yamazaki
DRUG METABOLISM AND DISPOSITION
(2020)