Laboratory of Cellular Therapy G. Lanzani, USC Haematology, Ospedali Riuniti, Bergamo, Italy.
Arch Biochem Biophys. 2012 Oct 15;526(2):146-53. doi: 10.1016/j.abb.2012.02.011. Epub 2012 Feb 25.
Therapeutic monoclonal antibodies (mAbs) are mostly used in cancer, as anti-infectious agents and as immunomodulatory drugs, and are amongst the most active area of research and development in the pharmaceutical industry. This class of drugs comprises unconjugated antibodies or antibody fragments, antibody-drug conjugates, radio-immunoconjugates and bispecific/trispecific molecules. A better understanding of the mechanism of action of successful mAbs is fundamental for the selection of more active and less toxic mAbs of new generation. Furthermore reliable screening of new compounds at an early stage of preclinical development, for both efficacy and toxicity, should allow the selection of the best molecules at an early stage, and improve the rate of success of this class of drugs. Here we review the major methods that are employed for testing the activity of therapeutic mAbs in vitro and in vivo in small animal models and point out to some of the pitfalls in these assays.
治疗性单克隆抗体（mAbs）主要用于癌症、抗感染药物和免疫调节药物，是制药行业最活跃的研究和开发领域之一。这类药物包括未缀合的抗体或抗体片段、抗体药物偶联物、放射免疫偶联物和双特异性/三特异性分子。更好地了解成功的 mAbs 的作用机制对于选择新一代更有效和毒性更低的 mAbs 至关重要。此外，在临床前开发的早期阶段，对新化合物进行疗效和毒性的可靠筛选，应该能够在早期选择出最佳分子，提高这类药物的成功率。在这里，我们回顾了用于在小动物模型中体外和体内测试治疗性 mAbs 活性的主要方法，并指出了这些测定中的一些缺陷。
