Deyev Sergey M, Lebedenko Ekaterina N
Russian Academy of Sciences, Shemyakin/Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
Bioessays. 2008 Sep;30(9):904-18. doi: 10.1002/bies.20805.
High-precision tumor targeting with conventional therapeutics is based on the concept of the ideal drug as a "magic bullet"; this became possible after techniques were developed for production of monoclonal antibodies (mAbs). Innovative DNA technologies have revolutionized this area and enhanced clinical efficiency of mAbs. The experience of applying small-size recombinant antibodies (monovalent binding fragments and their derivatives) to cancer targeting showed that even high-affinity monovalent interactions provide fast blood clearance but only modest retention time on the target antigen. Conversion of recombinant antibodies into multivalent format increases their functional affinity, decreases dissociation rates for cell-surface and optimizes biodistribution. In addition, it allows the creation of bispecific antibody molecules that can target two different antigens simultaneously and do not exist in nature. Different multimerization strategies used now in antibody engineering make it possible to optimize biodistribution and tumor targeting of recombinant antibody constructs for cancer diagnostics and therapy.
使用传统疗法进行高精度肿瘤靶向是基于理想药物作为“神奇子弹”的概念；在开发出单克隆抗体（mAb）生产技术后，这才成为可能。创新的DNA技术彻底改变了这一领域，并提高了单克隆抗体的临床效率。将小尺寸重组抗体（单价结合片段及其衍生物）应用于癌症靶向的经验表明，即使是高亲和力的单价相互作用也会导致血液快速清除，但在靶抗原上的保留时间仅适度。将重组抗体转化为多价形式可增加其功能亲和力，降低细胞表面的解离速率并优化生物分布。此外，它还允许创建双特异性抗体分子，这些分子可以同时靶向两种不同的抗原，而自然界中并不存在。目前抗体工程中使用的不同多聚化策略使得优化重组抗体构建体的生物分布和肿瘤靶向用于癌症诊断和治疗成为可能。
