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首页> 外文期刊>British Journal of Haematology >Phage display generation of a novel human anti-CD1A monoclonal antibody with potent cytolytic activity
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Phage display generation of a novel human anti-CD1A monoclonal antibody with potent cytolytic activity

机译:噬菌体展示一种新型人抗CD1A单克隆抗体,具有有效的细胞溶解活性

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摘要

CD1A is a cell surface protein expressed on Langerhans cells and cortical thymocytes that could potentially be used as an immunotherapeutic target in Langerhans Cell Histiocytosis (LCH), the cortical subtype of T-cell acute lymphocytic leukaemia (T-ALL) and other CD1A-positive tumours. The monoclonal antibody (mAb) CR2113 was selected from a panel of six fully human mAbs isolated from a semi-synthetic phage display library, based on specificity and avidity against cells expressing CD1 antigen variants. CR2113 recognized CD1A in T-ALL cell lines and patient samples. Confocal microscopy revealed that the CR2113-CD1A complex was internalized at 37°C. Furthermore, while CR2113 induced moderate complement-dependent cytotoxicity (CDC), potent antibody-dependent cell cytotoxicity (ADCC) activity was observed against CD1A expressing cell lines as well as T-ALL cell lines and T-ALL patient samples. In vivo experiments showed that CR2113 as a naked antibody has modest but specific anti-tumour activity against CD1A-expressing tumours. CR2113 is a high-affinity human anti-CD1A mAb with significant ADCC activity. These properties make CR2113 a candidate for clinical diagnostic imaging and therapeutic targeting of LCH as well as potential use in other clinical applications.
机译:CD1A是在朗格汉斯细胞和皮质胸腺细胞上表达的细胞表面蛋白,其可能被用作朗格汉斯细胞组织菌(LCH)中的免疫治疗靶标,T细胞急性淋巴细胞白血病(T-All)和其他CD1A阳性的皮质亚型肿瘤。基于表达CD1抗原变体的细胞的特异性和亲和力,单克隆抗体(MAB)CR2113选自来自半合成噬菌体展示文库的六个全人mAb。 CR2113在T-all细胞系和患者样品中识别CD1a。共聚焦显微镜显示CR2113-CD1A络合物在37℃下内化。此外,虽然CR2113诱导的中等补体依赖性细胞毒性(CDC),但是,对表达CD1A表达CD1A以及T-所有细胞系和T-所有患者样品,观察到有效的抗体依赖性细胞细胞毒性(ADCC)活性。体内实验表明,作为裸抗体的CR2113具有适度但对表达CD1A表达肿瘤的抗肿瘤活性的适度但特异性的抗肿瘤活性。 CR2113是一种高亲和力人抗CD1A mAb,具有显着的ADCC活性。这些性质使CR2113成为临床诊断成像和LCH治疗靶向的候选者以及在其他临床应用中的潜在用途。

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