Baum Patrick, Müller Dafne, Rüger Ronny, Kontermann Roland E
Institut für Zellbiologie und Immunologie, Universität Stuttgart, Stuttgart, Germany.
J Drug Target. 2007 Jul;15(6):399-406. doi: 10.1080/10611860701453034.
Tumor stromal cells have gained increasing attention as possible target for cancer therapy. Fibroblast activation protein (FAP) represents a cell surface antigen selectively expressed by reactive tumor stromal fibroblasts of various cancers. Here, we describe anti-FAP immunoliposomes as carrier systems for active targeting of FAP-expressing cells. As targeting ligand we used single-chain Fv (scFv) molecules cross-reacting with human and mouse FAP. These scFv molecules were genetically modified to express an additional cysteine residue at the C-terminus allowing a defined and site-directed conjugation. Coupling to Mal-PEG(2000)-DSPE containing liposomes resulted in sterically stabilized scFv immunoliposomes showing strong and specific binding to FAP-expressing cells. These immunoliposomes were highly stable when incubated under physiological conditions (human plasma, 37 degrees C). In addition, we could show that binding to FAP-expressing cells leads to internalization of intact liposomes into the endosomal compartment. Thus, these anti-FAP scFv immunoliposomes should be suitable for target cell-specific delivery and uptake of encapsulated drugs.
肿瘤基质细胞作为癌症治疗的潜在靶点越来越受到关注。成纤维细胞活化蛋白（FAP）是一种细胞表面抗原，在各种癌症的反应性肿瘤基质成纤维细胞中选择性表达。在此，我们描述了抗FAP免疫脂质体作为靶向表达FAP细胞的载体系统。作为靶向配体，我们使用了与人及小鼠FAP交叉反应的单链Fv（scFv）分子。这些scFv分子经过基因改造，在C末端表达一个额外的半胱氨酸残基，以实现特定且定点的偶联。与含Mal-PEG(2000)-DSPE的脂质体偶联后，得到了空间稳定的scFv免疫脂质体，其对表达FAP的细胞具有强烈且特异性的结合。这些免疫脂质体在生理条件（人血浆，37℃）下孵育时高度稳定。此外，我们还表明，与表达FAP的细胞结合会导致完整脂质体内化进入内体区室。因此，这些抗FAP scFv免疫脂质体应适用于靶细胞特异性递送和摄取包封的药物。
