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首页> 外文期刊>Antibodies >Species-Dependent Functionality of the Human Cytolytic Fusion Proteins Granzyme B-H22(scFv) and H22(scFv)-Angiogenin in Macrophages
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Species-Dependent Functionality of the Human Cytolytic Fusion Proteins Granzyme B-H22(scFv) and H22(scFv)-Angiogenin in Macrophages

机译：人类细胞溶解性融合蛋白粒酶B-H22（scFv）和H22（scFv）-血管生成素在巨噬细胞中的物种依赖性功能。

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Human cytolytic fusion proteins (hCFPs) are comprised of a specific cell-surface-binding moiety and an effector molecule of human origin. In contrast to common immunotoxins, including bacterial or plant toxins, they are considered not to be immunogenic. Two examples for human pro-apoptotic effector proteins are the serine protease Granzyme B and the RNase Angiogenin. Pre-clinical testing of functionality in in vitro and in vivo studies is essential for therapeutics. Establishing relevant animal models that have predictive value for therapeutic success is a great challenge in biomedical research. In this study, we investigated the species-dependent cytotoxic activity of two hCFPs prior to their application in a murine inflammation model. We found that in vitro and ex vivo either hCFP was able to kill human cells only, leaving murine cells unaffected. In contrast, no species-dependency was found for the bacterial Pseudomonas exotoxin A based immunotoxin H22(scFv)-ETA’. This species-dependent functioning has to be carefully considered when performing pre-clinical studies in animal models.
机译：人类溶细胞融合蛋白（hCFP）由特定的细胞表面结合部分和人类起源的效应分子组成。与常见的免疫毒素（包括细菌或植物毒素）相反，它们被认为不是免疫原性的。人类促凋亡效应蛋白的两个例子是丝氨酸蛋白酶Granzyme B和RNase血管生成素。临床前的体外和体内研究功能测试对于治疗至关重要。建立对治疗成功具有预测价值的相关动物模型是生物医学研究中的巨大挑战。在这项研究中，我们调查了两种hCFPs在鼠类炎症模型中应用之前的物种依赖性细胞毒活性。我们发现，无论在体外还是在体外，hCFP都只能杀死人细胞，而鼠细胞不受影响。相比之下，没有发现细菌假单胞菌外毒素A型免疫毒素H22（scFv）-ETA’的物种依赖性。在动物模型中进行临床前研究时，必须仔细考虑这种依赖物种的功能。

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