Kiefer Jonathan D, Neri Dario
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland.
Immunol Rev. 2016 Mar;270(1):178-92. doi: 10.1111/imr.12391.
The activation of the immune system for a selective removal of tumor cells represents an attractive strategy for the treatment of metastatic malignancies, which cannot be cured by existing methodologies. In this review, we examine the design and therapeutic potential of immunocytokines and bispecific antibodies, two classes of bifunctional products which can selectively activate the immune system at the tumor site. Certain protein engineering aspects, such as the choice of the antibody format, are common to both classes of therapeutic agents and can have a profound impact on tumor homing performance in vivo of individual products. However, immunocytokines and bispecific antibodies display different mechanisms of action. Future research activities will reveal whether an additive of even synergistic benefit can be obtained from the judicious combination of these two types of biopharmaceutical agents.
激活免疫系统以选择性清除肿瘤细胞是治疗转移性恶性肿瘤的一种有吸引力的策略,而现有方法无法治愈此类肿瘤。在本综述中,我们研究了免疫细胞因子和双特异性抗体这两类双功能产品的设计及其治疗潜力,它们能够在肿瘤部位选择性激活免疫系统。某些蛋白质工程方面,例如抗体形式的选择,是这两类治疗药物共有的,并且会对单个产品在体内的肿瘤归巢性能产生深远影响。然而,免疫细胞因子和双特异性抗体具有不同的作用机制。未来的研究活动将揭示,通过明智地组合这两种生物制药剂,是否能够获得相加甚至协同的益处。