A novel human anti-interleukin-1β neutralizing monoclonal antibody showing in vivo efficacy.
A novel human anti-interleukin-1β neutralizing monoclonal antibody showing in vivo efficacy.
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作者：
Goh AX;Bertin-Maghit S;Ping Yeo S;Ho AW;Derks H;Mortellaro A;Wang CI
促炎症细胞因子白介素1β是许多涉及免疫系统失调的临床靶点；阻断白介素1β的治疗方法已被批准用于治疗类风湿性关节炎(RA)、新生儿起病的多系统炎症性疾病、低温比林相关的周期性综合征、活动性系统性幼年特发性关节炎。在这里，我们报道了一种新的全人抗体的产生和工程，该抗体与IL-1β紧密结合，中和效力比上市抗体Canakinumab高10倍以上。亲和力成熟后，衍生抗体与人IL-1β的亲和力是亲本抗体的30倍。这种抗人IL-1β免疫球蛋白还可以与小鼠和猴子的IL-1β发生交叉反应，从而促进临床前的发展。在许多小鼠模型中，这种抗体有效地减少或消除了与IL-1β病理相关的疾病迹象。由于其对细胞因子的高度亲和力以及在体外和体内的效力，我们认为这种新型的全人抗IL-1β单抗是一种有前途的治疗候选药物，是目前治疗手段的潜在替代品。
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.
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影响因子：
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作者：
Lawrence, Reva C.;Felson, David T.;Wolfe, Frederick
通讯作者：
Wolfe, Frederick
影响因子：
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通讯作者：
OLSON, AJ
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de Haard, HJ;van Neer, N;Hoogenboom, HR
通讯作者：
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NOVOTNY, J;BRUCCOLERI, RE;SAUL, FA
通讯作者：
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