ABSTRACT
Since the late 1990s, therapeutic antibodies have been developed for various oncology and immunoinflammatory diseases. To date, more than 100 therapeutic antibodies have been approved in Japan, the U.S., and Europe for these indications. In contrast, the development of antibody drugs in the field of infectious diseases has been limited so far. The recent SARS-CoV-2 pandemic has highlighted the importance of therapeutic antibodies for infectious diseases as well as the development of drug delivery systems（DDS）. This review summarizes the past development of antibody drugs for infectious diseases and provides a future perspective of how therapeutic antibodies can be developed by utilizing antibody engineering and DDS technologies.Alternate :抄録1990年代後半に、がん領域や免疫炎症性疾患領域において、抗体医薬品が画期的な治療効果を示して以降、さまざまな疾患領域において抗体医薬品の研究開発がなされ、現在までに日米欧で100品目を超える抗体医薬品が承認されている。感染症領域における抗体医薬品の開発は限られていたが、抗体工学の発展、SARS-CoV-2の感染の拡大により、感染症領域における抗体医薬品の重要性が注目されている。本稿では、これまでの感染症領域における抗体医薬品の開発と、抗体工学やDDS技術の進展に伴う今後の抗体医薬品の展望を概説する。
ABSTRACT
The emergence of escape variants of SARS-CoV-2 carrying mutations in the spike protein poses a challenge for therapeutic antibodies. Here, we show that through the comprehensive engineering of the variable region of the neutralizing monoclonal antibody 5A6, the engineered antibody, 5A6CCS1, is able to neutralize SARS-CoV-2 variants that escaped neutralization by the original 5A6 antibody. In addition to the improved affinity against variants, 5A6CCS1 was also optimized to achieve high solubility and low viscosity, enabling a high concentration formulation for subcutaneous injection. In cynomolgus monkeys, 5A6CCS1 showed a long plasma half-life and good subcutaneous bioavailability through engineering of the variable and constant region. These data demonstrate that 5A6CCS1 is a promising antibody for development against SARS-CoV-2 and highlight the importance of antibody engineering as a potential method to counteract escape variants.