Département de génie chimique, Université Laval, Québec, QC. Canada.
National Research Council Canada, Montréal, QC. Canada.
Curr Gene Ther. 2017;16(6):363-374. doi: 10.2174/1566523217666170102111251.
Monoclonal antibodies (mAbs) based-therapies are currently one of the most successful strategies to treat immune disorders, cancer and infectious diseases. Vectors derived from adenoassociated virus (AAV) are very attractive to deliver the genes coding the mAbs because they allow long-term expression thus, reducing the number of administrations. They can also penetrate biological barriers such as the blood-brain-barrier to transduce cells localized in immunoprivileged organs. Recent animal studies with AAV have demonstrated the capacity of AAV to deliver sufficient quantity of antibodies to confer an efficient immunoprotection against chronic and infectious diseases for several months to years. The treatment was successfully applied either for prophylaxis or therapeutic use, depending on the disease and its progression. In this review, we discuss the advantages and the limitations of AAV for mAb and immunoadhesin delivery. Recent advances in vector design and antibody engineering are also presented. Optimization of the vector design can improve the kinetic and the level of mAbs expression whereas protein engineering can enhance transgene product properties. Furthermore, an exhaustive review of pre-clinical studies for chronic diseases including Alzheimer disease, amyotrophic lateral sclerosis and cancer is presented as well as for infectious diseases.
单克隆抗体（mAbs）为基础的治疗方法是目前治疗免疫紊乱、癌症和传染病最成功的策略之一。腺相关病毒（AAV）载体在输送编码 mAbs 的基因方面非常有吸引力，因为它们允许长期表达，从而减少给药次数。它们还可以穿透血脑屏障等生物屏障，将免疫豁免器官中定位的细胞转导。最近的 AAV 动物研究表明，AAV 能够输送足够数量的抗体，在数月至数年的时间内提供有效的免疫保护，以预防和治疗慢性和传染性疾病。根据疾病及其进展，该治疗可成功用于预防或治疗。在这篇综述中，我们讨论了 AAV 用于 mAb 和免疫黏附素传递的优点和局限性。还介绍了载体设计和抗体工程的最新进展。优化载体设计可以提高 mAbs 的表达速度和水平，而蛋白质工程可以增强转基因产物的特性。此外，还对包括阿尔茨海默病、肌萎缩侧索硬化症和癌症在内的慢性疾病以及传染病的临床前研究进行了全面回顾。
