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一种针对表皮生长因子受体的小鼠/人嵌合抗体的表达与特性分析

Expression and characterization of a mouse/human chimeric antibody specific for EGF receptor.

作者信息

Ferrer C, Anastasi A M, Di Massimo A M, Bullo A, Di Loreto M, Raucci G, Pacilli A, Rotondaro L, Mauro S, Mele A, De Santis R

机构信息

Menarini Ricerche SpA, Department of Biotechnology, Pomezia, Rome, Italy.

出版信息

J Biotechnol. 1996 Nov 29;52(1):51-60. doi: 10.1016/s0168-1656(96)01625-2.

Abstract

Murine antibodies which recognize the epidermal growth factor receptor (EGF-r) are good candidates for therapy and diagnosis of tumors overexpressing this receptor. Here we report the isolation of the variable regions from a murine monoclonal antibody anti-EGF-r (Mint5), the procedure to obtain the mouse/human chimeric antibody (chMint5) and its expression in COS, NS0 and CHO cells. The approach followed to construct chMint5 is based on the use of consensus primers specific for the ends of the variable regions. The sequence imposed by the primers did not affect the targeting potential of the antibody. In fact, the affinity of the chimeric antibody for EGF-r was nearly the same as that of the parental murine antibody. Based on previous in vitro and in vivo animal studies. Mint5 was shown to be a good candidate for the targeting of EGF-r overexpressing tumours. chMint5 is expected to be less immunogenic than murine antibody and therefore, could be useful for human treatment.

摘要

识别表皮生长因子受体(EGF-r)的鼠源抗体是治疗和诊断过表达该受体肿瘤的良好候选物。在此,我们报告了从小鼠抗EGF-r单克隆抗体(Mint5)中分离可变区、获得小鼠/人嵌合抗体(chMint5)及其在COS、NS0和CHO细胞中表达的过程。构建chMint5所采用的方法基于使用针对可变区末端的共有引物。引物引入的序列并未影响抗体的靶向潜力。事实上,嵌合抗体对EGF-r的亲和力与亲本鼠源抗体几乎相同。基于先前的体外和体内动物研究,Mint5被证明是靶向过表达EGF-r肿瘤的良好候选物。预计chMint5的免疫原性低于鼠源抗体,因此可用于人类治疗。

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