Gerstmayer B, Hoffmann M, Altenschmidt U, Wels W
Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, Germany.
Cancer Immunol Immunother. 1997 Nov-Dec;45(3-4):156-8. doi: 10.1007/s002620050421.
T cells require at least two signals for activation and clonal expansion. The first signal conferring specificity is initiated by interaction of the T cell receptor with peptide-bearing MHC molecules. The second, costimulatory signal can be provided by cell-surface molecules on antigen-presenting cells such as B7-1 (CD80) and B7-2 (CD86), which interact with CD28 on T cells. To direct the costimulatory B7-2 molecule to the surface of tumor cells we have constructed a chimeric fusion protein, which consists of the extracellular domain of human B7-2 fused to a single-chain antibody domain (scFv) specific for the ErbB2 protein, a type I growth factor receptor overexpressed in a high percentage of human adenocarcinomas. This B7-2(225)-scFv(FRP5) molecule, expressed in the yeast Pichia pastoris and purified from culture supernatants, binds to B7 counter-receptors and to ErbB2. B7-2(225)-scFv(FRP5) localizes specifically to the surface of ErbB2-expressing target cells, thereby providing a costimulatory signal, which results in enhanced proliferation of syngeneic T cells.
T细胞激活和克隆扩增至少需要两个信号。赋予特异性的第一个信号由T细胞受体与携带肽的MHC分子相互作用引发。第二个共刺激信号可由抗原呈递细胞上的细胞表面分子提供，如B7-1（CD80）和B7-2（CD86），它们与T细胞上的CD28相互作用。为了将共刺激B7-2分子导向肿瘤细胞表面，我们构建了一种嵌合融合蛋白，它由人B7-2的胞外结构域与对ErbB2蛋白特异的单链抗体结构域（scFv）融合而成，ErbB2是一种I型生长因子受体，在高比例的人腺癌中过表达。这种在巴斯德毕赤酵母中表达并从培养上清液中纯化的B7-2(225)-scFv(FRP5)分子，能与B7反受体以及ErbB2结合。B7-2(225)-scFv(FRP5)特异性定位于表达ErbB2的靶细胞表面，从而提供共刺激信号，导致同基因T细胞增殖增强。
