Kleinschmidt Martin, Rudolph Rainer, Lilie Hauke
Institut für Biotechnologie, Martin-Luther-Universitat, Universität Halle, Kurt-Mothes Strasse 3, Germany.
J Mol Biol. 2003 Mar 21;327(2):445-52. doi: 10.1016/s0022-2836(03)00141-4.
Immunotoxins are genetically engineered fusion proteins of an antibody Fv fragment and a toxin from bacteria or plants, which function as anti-cancer therapeutics. Here, we describe a new generation of immunotoxins in which both proteins do not form a single fusion protein but are coupled specifically via cysteine-containing polyionic fusion peptides. The engineered Pseudomonas exotoxin PE38 was N-terminally fused to the peptide E(8)C. In combination with the disulfide-stabilized Fv fragment of the tumor-specific antibody B3, which was extended by the peptide R(8)CP, the fusion peptides ensured a specific and covalent coupling of the Fv fragment and the toxin. The resulting immunotoxin was as active and as specific as an immunotoxin consisting of a fusion protein of the same antibody fragment connected to the toxin.
免疫毒素是一种通过基因工程构建的融合蛋白，由抗体Fv片段与细菌或植物来源的毒素组成，可作为抗癌治疗药物。在此，我们描述了新一代的免疫毒素，其中这两种蛋白并非形成单一融合蛋白，而是通过含半胱氨酸的聚离子融合肽特异性偶联。工程改造的绿脓杆菌外毒素PE38在N端与肽E(8)C融合。与肿瘤特异性抗体B3的二硫键稳定Fv片段（该片段由肽R(8)CP进行延伸）相结合，这些融合肽确保了Fv片段与毒素之间的特异性共价偶联。所得到的免疫毒素与由相同抗体片段与毒素的融合蛋白组成的免疫毒素具有相同的活性和特异性。
