Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice
Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice
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DOI：
10.1016/s0022-1759(99)00154-4
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发表时间：
1999-12-10
影响因子：
2.2
通讯作者：
Rybak, SM
中科院分区：
文献类型：
--
作者：
Newton, DL;Pollock, D;Rybak, SM
与人类酶融合的抗体提供了一种与植物或细菌毒素结合的抗体特异性靶向肿瘤的替代方案。由于大量使用这些试剂不会引起非特异性毒性，因此需要有效的生产方法。本工作的目的是在转基因小鼠的乳腺中表达一种复杂的免疫酶融合蛋白（免疫毒素）。一种针对人转铁蛋白受体（E6）的鼠/人嵌合抗体在其CH2结构域与人血管生成核糖核酸酶angiogenin （Ang）基因融合。它在小鼠乳腺中表达并分泌到小鼠乳汁中。在牛奶中的表达水平约为0.8 g/l。嵌合蛋白保留了与游离Ang相当的抗体结合活性和蛋白质合成抑制活性。体外对人肿瘤细胞具有特异性细胞毒性。(C) 1999 Elsevier Science B.V.版权所有
Antibodies fused to human enzymes offer an alternative to specifically targeting tumors with antibodies linked to plant or bacterial toxins. Since large amounts of these reagents can be administered without eliciting non-specific toxicities, efficient methods of production are needed. The goal of this work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It was expressed in the mammary gland of mice and secreted into mouse milk. Expression levels in milk were approximately 0.8 g/l. The chimeric protein retained antibody binding activity and protein synthesis inhibitory activity equivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro. (C) 1999 Elsevier Science B.V. All rights reserved.