Ryffel B
Institute of Pathology, University of Basel, Switzerland.
Biomed Environ Sci. 1997 Mar;10(1):65-72.
Recombinant human proteins play an important role in therapy, especially in stimulating the hematopoiesis after chemotherapy, e.g., erythropoietin and colony stimulating factors, while several promising candidates such as IL-6, IL-12, thrombopoietin and others are in clinical development. Since the recombinant proteins are copies of endogenous proteins, it was assumed that they would be well tolerated. While this assumption is correct for some, other proteins proved to be less well tolerated. Therefore, preclinical safety assessment of these proteins is necessary. Based on the experience with several proteins, some guidance for the safety assessment can be given. Furthermore, data are presented demonstrating that preclinical toxicity studies may have a predictive value for man. Limitations of the classical approach of safety tests and new concepts are discussed.
重组人蛋白在治疗中发挥着重要作用，尤其是在化疗后刺激造血方面，例如促红细胞生成素和集落刺激因子，而一些有前景的候选药物如白细胞介素 -6、白细胞介素 -12、血小板生成素等正在进行临床开发。由于重组蛋白是内源性蛋白的拷贝，人们曾认为它们会具有良好的耐受性。虽然这一假设对某些蛋白是正确的，但其他蛋白的耐受性却较差。因此，对这些蛋白进行临床前安全性评估是必要的。基于对几种蛋白的经验，可以给出一些安全性评估的指导。此外，还展示了数据，表明临床前毒性研究可能对人类具有预测价值。同时讨论了经典安全性测试方法的局限性和新概念。
