Fc-based therapeutics including therapeutic full-size monoclonal antibodies (mAbs) and Fcfusion
proteins represent fastest-growing market in biopharmaceutical industrial. However, one major
challenge during development of Fc-based therapeutics is how to maintain their efficacy in clinic use.
Many factors may lead to failure in final marketing. For example, the stability and aggregation resistance
might not be high enough for bearing the disadvantages during fermentation, purification, formulation,
storage, shipment and other steps in manufacture and sale. Low stability and high aggregation
tendency lead to decreased bioactivity and increased risk of immunogenicity resulting in serious side
effect. Because Fc is one of the major parts in monoclonal antibodies and Fc-fusion proteins, engineering
of Fc to increase its stability and reduce or eliminate aggregation due to incorrect association are of
great importance and could further extend the potential of Fc-based therapeutics. Lots of studies focus
on Fc optimization for better physical and chemical characteristics and function by structured-based
computer-aid rational design, high-throughput screening expression system selection and other methods.
The identification of optimized Fc mutants increases the clinic potential of currently existed therapeutics
mAbs and Fc-fusion proteins, and accelerates the development of new Fc-based therapeutics. Here
we provide an overview of the related field, and discuss recent advances and future directions in optimization
of Fc-based therapeutics with modified stability and aggregation resistance.
Keywords: Fc, monoclonal antibody, Fc-fusion protein, stability, aggregation.
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