Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
[Feature articles] “Evolution of antibody-drug conjugates” Editor: Shino Manabe
Antibody engineering approaches toward optimization of antibody-drug conjugates
Hiroki AkibaHiroaki Ohno
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JOURNAL FREE ACCESS

2025 Volume 40 Issue 5 Pages 340-349

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Abstract
In this chapter, we discuss antibody engineering-based ADC optimization strategies and their future directions. Development of antibody drug conjugates(ADC) started from the optimization of the payload and linker. Today, antibody engineering has emerged as another option in optimization strategy. Bispecific antibodies have shown success in promoting cell internalization of ADC which leads to efficient payload release. Biparatopic antibodies binding two different epitopes of an antigen also promote cell internalization by the formation of bridged structures on the cell membrane, and several biparatopic ADCs are under clinical trials. While studying effective design of biparatopic antibodies, we designed a platform which leads to the development of novel two-component types of ADC. In addition to these bispecific approaches, control of antigen binding ability is also of interest. These engineering approaches will expand the potential of ADCs for variety of diseases.
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© 2025 The Japan Society of Drug Delivery System
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