Newton D L, Pollock D, DiTullio P, Echelard Y, Harvey M, Wilburn B, Williams J, Hoogenboom H R, Raus J C, Meade H M, Rybak S M
Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
J Immunol Methods. 1999 Dec 10;231(1-2):159-67. doi: 10.1016/s0022-1759(99)00154-4.
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.
与人类酶融合的抗体为利用与植物或细菌毒素相连的抗体特异性靶向肿瘤提供了一种替代方法。由于可以大量施用这些试剂而不会引发非特异性毒性，因此需要高效的生产方法。这项工作的目标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）的嵌合小鼠/人抗体在其CH2结构域与一种人血管生成核糖核酸酶血管生成素（Ang）的基因融合。它在小鼠乳腺中表达并分泌到小鼠乳汁中。乳汁中的表达水平约为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。它在体外对人肿瘤细胞具有特异性细胞毒性。
