Vitaliti A, Wittmer M, Steiner R, Wyder L, Neri D, Klemenz R
Department of Pathology, University Hospital, Zurich, Switzerland.
Cancer Res. 2000 Aug 15;60(16):4311-4.
Monoclonal antibody (Ab) directed against the vascular endothelial growth factor, one of the major inducers of angiogenesis, can inhibit tumor growth in mice. Treatment of cancer patients with monoclonal Ab requires large-scale production of the clean Ab and frequent application of the Ab. This might be improved by using single-chain Ab fragments (scFvs), which can be produced in large quantities in bacteria and are attractive for gene therapeutic approaches. Here we describe anti-vascular endothelial growth factor scFvs derived from a human phage-display library able to block the vascularization of the chorioallantoic membrane of chick embryos and reduce the growth of s.c. tumors in nude mice. This work opens the way to develop gene therapy-based strategies using a scFv to treat angiogenesis-dependent diseases.
针对血管内皮生长因子(血管生成的主要诱导因子之一)的单克隆抗体可抑制小鼠肿瘤生长。用单克隆抗体治疗癌症患者需要大规模生产纯净抗体并频繁应用该抗体。使用单链抗体片段(scFv)可能会改善这种情况,scFv可在细菌中大量生产,对基因治疗方法具有吸引力。在此,我们描述了从人噬菌体展示文库中获得的抗血管内皮生长因子scFv,它能够阻断鸡胚绒毛尿囊膜的血管化,并减少裸鼠皮下肿瘤的生长。这项工作为开发基于基因治疗的策略(使用scFv治疗血管生成依赖性疾病)开辟了道路。