A novel human anti-interleukin-1β neutralizing monoclonal antibody showing in vivo efficacy. 2014

Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
Singapore Immunology Network; Agency for Science; Technology and Research (A*STAR); Singapore.

The pro-inflammatory cytokine interleukin (IL)-1β is a clinical target in many conditions involving dysregulation of the immune system; therapeutics that block IL-1β have been approved to treat diseases such as rheumatoid arthritis (RA), neonatal onset multisystem inflammatory diseases, cryopyrin-associated periodic syndromes, active systemic juvenile idiopathic arthritis. Here, we report the generation and engineering of a new fully human antibody that binds tightly to IL-1β with a neutralization potency more than 10 times higher than that of the marketed antibody canakinumab. After affinity maturation, the derived antibody shows a>30-fold increased affinity to human IL-1β compared with its parent antibody. This anti-human IL-1β IgG also cross-reacts with mouse and monkey IL-1β, hence facilitating preclinical development. In a number of mouse models, this antibody efficiently reduced or abolished signs of disease associated with IL-1β pathology. Due to its high affinity for the cytokine and its potency both in vitro and in vivo, we propose that this novel fully human anti-IL-1β monoclonal antibody is a promising therapeutic candidate and a potential alternative to the current therapeutic arsenal.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D010538 Peritonitis INFLAMMATION of the PERITONEUM lining the ABDOMINAL CAVITY as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the PERITONEAL CAVITY via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the ABDOMINAL CAVITY itself through RUPTURE or ABSCESS of intra-abdominal organs. Primary Peritonitis,Secondary Peritonitis,Peritonitis, Primary,Peritonitis, Secondary
D003429 Cross Reactions Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen. Cross Reaction,Reaction, Cross,Reactions, Cross
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females

Related Publications

Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
June 2012, Clinical pharmacokinetics,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
November 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
January 2015, The Journal of infectious diseases,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
December 2017, Antiviral research,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
September 1998, Journal of virological methods,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
July 2015, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
August 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
March 2017, Cancer science,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
January 2015, mAbs,
Angeline X H Goh, and Sebastien Bertin-Maghit, and Siok Ping Yeo, and Adrian W S Ho, and Heidi Derks, and Alessandra Mortellaro, and Cheng-I Wang
February 2008, Experimental & molecular medicine,
Copied contents to your clipboard!