Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA.
BioDrugs. 2020 Jun;34(3):273-293. doi: 10.1007/s40259-020-00412-3.
Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others.
抗体免疫疗法正在彻底改变现代医学。在过去的 40 年中,该领域取得了巨大的进展,部分原因是分离和制造技术的重大进步,这些技术使这些重要的生物制剂成为现代医学的前沿。然而,单克隆抗体 (mAb) 生物制剂的全球应用受到生物物理和生化缺陷、生产限制、对冷链储存和运输的需求以及制造和分销成本高昂的阻碍。这些障碍中的一些可以通过瞬时体内基因传递平台来克服,例如经过工程设计以编码优化的 mAb 基因的非病毒合成质粒 DNA 和信使 RNA 载体。这些方法将身体变成了抗体生产的生物工厂,消除了生物工艺中涉及的许多步骤,并提供了其他几个重要优势,与传统的基因治疗(永久性传递)方法不同。在这篇综述中,我们专注于使用合成质粒 DNA 载体平台和 RNA 传递的抗体核酸传递,这些都是重要的方法,正在推进简单、快速的体内表达,并在传染病和癌症等动物模型中产生影响。