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在肿瘤部位递送细胞因子:免疫细胞因子偶联的抗EDB-纤连蛋白抗体的案例。

Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case.

作者信息

Ronca Roberto, Sozzani Silvano, Presta Marco, Alessi Patrizia

机构信息

Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.

出版信息

Immunobiology. 2009;214(9-10):800-10. doi: 10.1016/j.imbio.2009.06.005. Epub 2009 Jul 21.

Abstract

Although considerable efforts have been made in the discovery of new agents for cancer treatment, several promising therapeutics cannot be applied systemically because of their severe side effects. This is the case for various recombinant pro-inflammatory cytokines that, despite their potent anti-cancer activity, can not find their way to clinical exploitation due to their devastating toxicity shown during dose escalation to therapeutically active concentrations. To circumvent these problems, an elegant and efficient way to accumulate therapeutic agents at the tumor site, thus reducing systemic side effects, is their conjugation to tumor-specific antibodies. Here, we review preclinical data about immunocytokines conjugated to a promising single-chain human antibody that selectively targets tumor-associated stroma and blood vessels by binding with high affinity and specificity to the extra domain-B (EDB) of fibronectin.

摘要

尽管在发现用于癌症治疗的新药物方面已经付出了巨大努力,但由于几种有前景的治疗药物具有严重的副作用,无法进行全身应用。各种重组促炎细胞因子就是这种情况,尽管它们具有强大的抗癌活性,但在剂量递增至治疗活性浓度时显示出的毁灭性毒性,使其无法应用于临床。为了规避这些问题,一种在肿瘤部位积累治疗药物从而减少全身副作用的巧妙而有效的方法,是将它们与肿瘤特异性抗体偶联。在此,我们综述了关于与一种有前景的单链人抗体偶联的免疫细胞因子的临床前数据,该单链人抗体通过与纤连蛋白的额外结构域B(EDB)高亲和力和特异性结合,选择性地靶向肿瘤相关基质和血管。

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