Article
Immunology
Bruce D. Wines, Halina M. Trist, Sandra Esparon, Rachael E. Impey, Graham A. Mackay, Robert K. Andrews, Tatiana P. Soares da Costa, Geoffrey A. Pietersz, Ross Baker, P. Mark Hogarth
Summary: The activation of Fc gamma RIIa by monoclonal antibodies requires interaction with both the Fab and Fc regions simultaneously on the same receptor molecules.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Simone I. I. Richardson, Frances Ayres, Nelia P. P. Manamela, Brent Oosthuysen, Zanele Makhado, Bronwen E. E. Lambson, Lynn Morris, Penny L. L. Moore
Summary: The study revealed that IgG3 bNAbs demonstrate stronger protective ability and phagocytosis against HIV infection, especially against certain specific HIV strains, indicating that altering the constant region of antibodies may enhance their neutralizing and Fc effector activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Adrian Elter, Desislava Yanakieva, David Fiebig, Kerstin Hallstein, Stefan Becker, Ulrich Betz, Harald Kolmar
Summary: This study introduces a novel Fc-tamed antibody format, which reduces off-target toxicity by blocking the Fc gamma R-binding sites of antibodies, resulting in decreased activation and improved safety profiles.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Chunyu Liu, Chuanfei Yu, Yalan Yang, Jing Huang, Xiaojuan Yu, Maoqin Duan, Lang Wang, Junzhi Wang
Summary: In this study, an engineered monoclonal Jurkat/NFAT/CD32a-Fc epsilon RI gamma effector cell line was developed to measure the bioactivity of antibody-dependent cellular phagocytosis (ADCP). The bioassay was optimized using a Design of Experiment (DoE) strategy and fully validated according to ICH-Q2(R1) to demonstrate good performance characteristics. The established bioassay can be applied to evaluate the ADCP bioactivity for anti-CD20 mAbs and potentially for mAbs targeting other antigens.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Patricia Gogesch, Simone Dudek, Ger van Zandbergen, Zoe Waibler, Martina Anzaghe
Summary: Efforts have been made to ensure the safety and efficacy of therapeutic monoclonal antibodies since the approval of the first mAb in 1986. Various cell-based assays have been established to evaluate Fc-mediated effector functions of therapeutic mAbs. Optimization strategies such as point mutations and altered glycosylation patterns have led to the development of next-generation therapeutic mAbs with improved efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Ahmed M. Khalil, Michael S. Piepenbrink, Ian Markham, Madhubanti Basu, Luis Martinez-Sobrido, James J. Kobie
Summary: IBV contributes significantly to morbidity and mortality, particularly in children, necessitating improvements in vaccines and treatments. A specific hMAb, 1092D4, has been found to have minimal dependence on Fc-effector functions for in vivo antiviral activity.
Article
Biochemistry & Molecular Biology
Yannic C. Bartsch, Deniz Cizmeci, Jaewon Kang, Tomer Zohar, Sivakumar Periasamy, Nickita Mehta, Jeroen Tolboom, Leslie Van der Fits, Jerry Sadoff, Christy Comeaux, Benoit Callendret, Alexander Bukreyev, Douglas A. Lauffenburger, Arangassery Rosemary Bastian, Galit Alter
Summary: RSV infection is a major cause of severe respiratory tract infection and death in infants and the elderly. This study found that protection against RSV infection is linked to opsonophagocytic functions driven by IgA and differentially glycosylated RSV-specific IgG profiles, indicating the importance of functional humoral immune response in preventing RSV.
Article
Immunology
Wenbo Wang, Chuanfei Yu, Yongfei Cui, Chunyu Liu, Yalan Yang, Gangling Xu, Gang Wu, Jialiang Du, Zhihao Fu, Luyong Guo, Caifeng Long, Xijie Xia, Yuhua Li, Lan Wang, Youchun Wang
Summary: Rabies is a fatal viral disease, and post-exposure prophylaxis is effective in preventing it. Research has shown that antibodies not only neutralize viruses, but also exert antiviral effects through ADCC. A novel method for evaluating the ADCC activity of anti-rabies antibodies has been developed.
MICROBIOLOGY AND IMMUNOLOGY
(2023)
Article
Chemistry, Analytical
Meng Li, Lan Wang, Chuanfei Yu, Junzhi Wang
Summary: The study established a reporter gene assay system based on the OX40-NF kappa B pathway to determine the bioactivity of anti-OX40 monoclonal antibodies. By crosslinking the Fc of the antibodies with OX40, the NF kappa B pathway was activated to evaluate the bioactivity of the antibodies.
Article
Chemistry, Analytical
Xiaojuan Yu, Chuanfei Yu, Kaiqin Wang, Chunyu Liu, Lan Wang, Junzhi Wang
Summary: Type 2 inflammatory cytokines play a significant role in the pathogenesis of asthma, and anti-IL-4R monoclonal antibody has been approved for therapeutic treatment. Researchers developed a bioactivity determination method based on RGA, which demonstrated excellent performance characteristics for anti-IL-4R mAbs through careful optimization of parameters.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Immunology
Julie M. Fox, Vicky Roy, Bronwyn M. Gunn, Glen R. Bolton, Daved H. Fremont, Galit Alter, Michael S. Diamond, Austin W. Boesch
Summary: This study demonstrates that enhancing Fc effector functions can improve the therapeutic activity of CHIKV-specific IgG. By using Fc?RIIIa affinity chromatography, enriched IgG with afucosylated glycoforms showed enhanced Fc effector functions and reduced viral load in mice infected with CHIKV.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Ruixiao Du, Chaoqiang An, Xin Yao, Yiping Wang, Ge Wang, Fan Gao, Lianlian Bian, Yalin Hu, Siyuan Liu, Qiaohui Zhao, Qunying Mao, Zhenglun Liang
Summary: In this study, an anti-CA16 monoclonal antibody (DMA2017) was generated from an epidemic strain of CA16. Although DMA2017 could not neutralize the original and circulating CA16 strains in vitro, it was found to protect suckling mice from a lethal challenge with CA16 in vivo through Fc-dependent effector functions. The linear epitope of DMA2017 was mapped to a conserved patch of residues 143-148 (NSHPPY) on the VP2 EF-loop of CA16. This research highlights the potential preventive and therapeutic effect of non-neutralizing antibodies and provides insights for the design and evaluation of CA16 vaccines.
EMERGING MICROBES & INFECTIONS
(2023)
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)
Article
Oncology
Huiting Wu, Chang Liu, Qiang Yuan, Yan Qiao, Yongwei Ding, Lina Duan, Wenjing Li, Mengjia Zhang, Xuhua Zhang, Yanan Jiang, Jing Lu, Ziming Dong, Tao Wang, Kangdong Liu, Jimin Zhao
Summary: In this study, a humanized and Fc-engineered anti-B7-H3 mAb 24F-Hu-mut2 was developed and its anti-tumor activity was systematically evaluated in vitro and in vivo. The results showed significant anti-ESCC activity of 24F-Hu-mut2. A computational docking model and ELISA results confirmed the binding of the mAb to specific domains of B7-H3. This study suggests that 24F-Hu-mut2 may be a promising antibody for treating ESCC and other B7-H3 overexpressing tumors.
Article
Genetics & Heredity
Hannes Vietzen, Vera Danklmaier, Alexander Zoufaly, Elisabeth Puchhammer-Stockl
Summary: This study investigates the role of genetic variants in activating natural killer (NK) cell receptors in contributing to the severity of COVID-19. The study shows that the high-affinity variant of the Fc gamma RIIIa receptor is over-represented in hospitalized and deceased patients with COVID-19, while the low-affinity variant is more common in patients with mild COVID-19. Additionally, functional assays reveal that hospitalized patients with COVID-19 exhibit significantly higher proinflammatory ADCC responses, particularly in NK cells expressing the high-affinity variant of the Fc gamma RIIIa receptor.
GENETICS IN MEDICINE
(2022)