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基于定量生物分布数据的双特异性抗体肿瘤靶向特性的评价。

A critical evaluation of the tumor-targeting properties of bispecific antibodies based on quantitative biodistribution data.

机构信息

Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.

出版信息

Protein Eng Des Sel. 2012 Dec;25(12):851-4. doi: 10.1093/protein/gzs061. Epub 2012 Sep 12.

DOI:10.1093/protein/gzs061
PMID:22972762
Abstract

Bispecific and bifunctional antibodies are attracting considerable interest as innovative anti-cancer therapeutics, but their ability to selectively localize at the tumor site has rarely been studied by quantitative biodistribution studies in immunocompetent animal models or in patients. Here, we describe the production of a novel bifunctional antibody, consisting of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin) fused to the extracellular portion of CD86 (co-stimulatory molecule B7.2). However, the fusion molecule was unable to target tumors in vivo. These data suggest that bispecific antibodies do not always localize on tumors and should therefore be characterized by imaging or biodistribution studies.

摘要

双特异性和双功能抗体作为创新的抗癌治疗药物引起了相当大的关注,但它们在免疫功能正常的动物模型或患者中通过定量生物分布研究选择性地定位于肿瘤部位的能力很少被研究。在这里,我们描述了一种新型双功能抗体的生产,该抗体由 F8 抗体(特异性针对纤连蛋白的交替剪接 EDA 结构域)与 CD86(共刺激分子 B7.2)的细胞外部分融合而成。然而,融合分子无法在体内靶向肿瘤。这些数据表明,双特异性抗体并不总是定位于肿瘤上,因此应该通过成像或生物分布研究进行表征。

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