a Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461;
Radiat Res. 2014 Aug;182(2):230-8. doi: 10.1667/RR13667.1. Epub 2014 Jul 8.
Recent advances indicate that new therapeutic strategies for the treatment of malignancies will be realized from combined radiation treatment and immune checkpoint modulation. Numerous biophysical properties must be considered for effective biologic development, including affinity, selectivity, oligomeric state and valency. High-resolution structural characterization contributes to our understanding of these properties and can lead to the realization of proteins with unique in vitro activities and novel in vivo therapeutic functions. In this article we focus on the importance of these factors for new potential biologics and consider these in the context of combination therapies with physical modalities, including radiation therapy. In particular, we examine the consequences of altered avidities and subset-specific ligand density on the rational modification of biological function in the immunoglobulin and tumor necrosis factor superfamilies and for new optimized combination therapies.
最近的进展表明，通过联合放射治疗和免疫检查点调节，将实现治疗恶性肿瘤的新治疗策略。为了有效的生物开发，必须考虑许多生物物理特性，包括亲和力、选择性、寡聚状态和价态。高分辨率结构表征有助于我们理解这些特性，并可以导致具有独特体外活性和新型体内治疗功能的蛋白质的实现。在本文中，我们重点讨论了这些因素对新的潜在生物制剂的重要性，并考虑了它们与物理治疗模式（包括放射治疗）联合治疗的情况。特别是，我们研究了改变亲和力和亚群特异性配体密度对免疫球蛋白和肿瘤坏死因子超家族中生物功能的合理修饰以及新的优化联合治疗的影响。
