A5072214339- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Asthma and respiratory diseases
- Immunotherapy and Immune Responses
- Allergic Rhinitis and Sensitization
- Mast cells and histamine
- Urticaria and Related Conditions
- Food Allergy and Anaphylaxis Research
- Blood groups and transfusion
- Complement system in diseases
- Cancer Immunotherapy and Biomarkers
- Dermatology and Skin Diseases
- Galectins and Cancer Biology
- Transgenic Plants and Applications
- Pharmaceutical studies and practices
Genomics Research Center, Academia Sinica
2009-2022
Academia Sinica
2011-2014
Institute of Molecular Medicine
2010
National Tsing Hua University
2008-2010
Over the last 2 decades, omalizumab is only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity mAb rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to of phase IIb but not III. This report features antigenic-functional characteristics UB-221, an newer class distinct from ligelizumab. free form, bound abundantly CD23-occupied IgE and, oligomeric mAb-IgE complex forms, freely engaged...
Anti-interferon (IFN)–γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on signaling unknown. Using single-cell capture method, we isolated 19 IFN-γ–reactive monoclonal antibodies (mAbs) from patients AIGAs. All displayed high-affinity (KD < 10−9 M) binding to IFN-γ, only eight neutralized IFN-γ–STAT1 HLA-DR expression. Signal blockade...
Abstract Membrane-bound IgE (mIgE) is part of the IgE–BCR and essential for generating isotype-specific responses. On mIgE+ B cells, membrane-bound ε-chain (mε) exists predominantly in long isoform, mεL, containing an extra 52 aa CεmX domain between CH4 C-terminal membrane-anchoring segment; short isoform mε, mεS, minor proportions. thus provides attractive site immunologic targeting cells. In this study, we show that nine newly prepared CεmX-specific mAbs, as well previously reported a20,...
Abstract Immunoglobulin E (IgE) antibodies play a central role in the allergic response: interaction with FcεRI on mast cells and basophils leads to immediate hypersensitivity reactions upon allergen challenge, while CD23/FcεRII, expressed variety of cells, regulates IgE synthesis among other activities. The receptor-binding IgE-Fc region has recently been found display remarkable flexibility, from acutely bent extended conformations, allosteric communication between distant CD23 binding...
Abstract In allergic patients sensitive to house dust mite allergens, the inhaled allergenic proteins are dissolved in mucosal fluid, cross epithelia of airway, and induce crosslinking FcεRI-bound allergen-specific IgE on mast cells basophils, leading degranulation those inflammatory cells. Our group has proposed that IgG, delivered airway mucosa, can bind incoming allergens preclude their entry into layer. this work, we prepared human monoclonal antibodies by isolating single B from with...
Abstract IgE is a primary mediator in most allergic diseases. Human specific for various allergens are very important reagents diagnostic assays the management of However, allergen-specific human IgEs present patients’ blood at low levels and hence extremely difficult to prepare. We have now constructed transgenic homozygous mouse strain, referred as HεκKI whose γ1 constant region gene segment has been replaced by ε κ gene. In those mice, about 10 times IgE. Upon immunization with an...
Abstract CεmX (also referred to as M1’) is a discrete domain of 52 a.a. residues, located between the CH4 and C-terminal membrane anchor peptide ε heavy chain membrane-bound IgE (mIgE) on human B lymphocytes. Antibodies that target are potentially useful in controlling production for treating allergic other IgE-mediated diseases. Herein we report an anti-CεmX mAb, 4B12, was shown be effective reducing allergen-specific IL-5 upon challenge allergen asthma model employing gene knocked-in mice...
Abstract CεmX (also referred to as M1’) is a discrete domain of 52 a.a. residues, located between the CH4 and C-terminal membrane anchor peptide ε heavy chain membrane-bound IgE (mIgE) on human B lymphocytes. Antibodies that target are potentially useful in controlling production for treating allergic other IgE-mediated diseases. Based its abilities bind mIgE with high affinity lyse mIgE-expressing lymphocytes by apoptosis, ADCC, cytolytic mechanisms, humanized 4B12 monoclonal antibody...
Abstract The mIgA is associated with Igα/Igβ as the B cell receptor (BCR) complex on mIgA-expressing cells. α chain of (mα), comparing to secreted IgA, contains an extra C-terminal membrane-anchor peptide, which encompasses extracellular, a transmembrane, and intracellular segments. extracellular segment, referred mIg isotype-specific (migis-α) segment or membrane proximal domain (EMPD), has been proposed specific antigenic site for targeting cells by antibodies. In this study, we developed...
Abstract CϵmX is a discrete domain of 52 a.a. residues, located between the CH4 and C-terminal membrane anchor peptide ϵ heavy chain membrane-bound IgE (mIgE) on human B cells. Among monoclonal antibodies (mAbs) prepared for their ability to bind fragments or CϵmX-containing recombinant proteins in ELISA, those that can native mIgE cells cause ADCC, apoptosis, other cytolytic mechanisms are potential useful controlling production treating allergic diseases. The CϵmX-specific mAbs previously...
Abstract IgE is a central mediator responsible for immediate-type hypersensitivity reactions. The anti-IgE monoclonal antibody (mAb), omalizumab, has been shown in numerous clinical trials to be efficacious the treatment of severe allergic asthma and other diseases. Omalizumab was designed bind free blood membrane-bound (mIgE) on B cells, but not bound by high-affinity Fc receptors (FcϵRI) basophils mast cells low-affinity (CD23) many cell types. Additionally, omalizumab can prevent it from...
Abstract On B lymphocytes, membrane-bound IgE (mIgE) is part of BCR and essential for generating isotype-specific response. mIgE+ cells in man, the ε chain (mε) exists predominantly long form (mεL), containing 52-a.a. CεmX domain between CH4 C-terminal membrane-anchoring segment; conventional mε (mεS) minor proportions. thus provides an attractive site immunological targeting cells. Here we have shown that 9 newly prepared CεmX-specific monoclonal antibodies (mAbs), as well previously...
Abstract The CεmX domain of 52 a.a. residues, located between the CH4 and membrane-anchor segment human membrane-bound ? chain on mIgE+ B cells, is a unique antigenic site for immunological targeting those cells. We have demonstrated that chimeric form anti-CεmX monoclonal antibody (mAb), 4B12, can induce apoptosis ADCC against mIgE.Fc+ cell transfectoma via effector cells from PBMC in vitro (presented by another abstract this meeting). To enhance clinical applicability we humanized it first...