Manache Lucie, Dulieu Claire, Boussif Otmane
Sanofi-Aventis R&D, Laboratoire de développement de formulation-biotech, département des sciences pharmaceutiques, 13, quai Jules Guesde, 94403, Vitry-sur-Seine, France.
Med Sci (Paris). 2009 Dec;25(12):1063-9. doi: 10.1051/medsci/200925121063.
Monoclonal antibodies and their derivatives such as antibody fragments, immunoconjugates and Fc fusions, represent the majority of therapeutic proteins in clinical development. Recent successes of such molecules in cancer and in the treatment of autoimmune diseases found a great hope in biotherapeutics. The progress in genetic engineering and in analytical development allowed the production of increasingly humanized antibodies, and thus less immunogenic. However the use of such molecules in therapeutics would not be possible without a good comprehension of their degradation pathways and therefore the development of formulations and manufacturing processes ensuring them a good stability along their production, shipment, storage and administration. The present review summarizes the key degradation pathways of monoclonal antibodies and the formulation approaches allowing a satisfactory shelf-life, ensuring both efficiency and safety of such biomedicines.
单克隆抗体及其衍生物，如抗体片段、免疫偶联物和Fc融合蛋白，占临床开发中治疗性蛋白质的大部分。这类分子最近在癌症和自身免疫性疾病治疗方面取得的成功为生物治疗带来了巨大希望。基因工程和分析技术的发展使得越来越多的人源化抗体得以生产，从而降低了免疫原性。然而，如果不能很好地理解它们的降解途径，就不可能在治疗中使用这类分子，因此也就无法开发出能确保它们在生产、运输、储存和给药过程中具有良好稳定性的制剂和生产工艺。本综述总结了单克隆抗体的关键降解途径以及能实现令人满意保质期的制剂方法，确保这类生物药物的有效性和安全性。
