The Analysis of Key Factors Related to ADCs Structural Design
Conclusion and Perspective With in-depth understandings of antibodies, linkers, and payloads, ADCs have also achieved great development. The linkage strategy and target diversity have already improved the delivery of the payloads to tumor tissues and reduced exposure to normal tissues. With the development of payloads, some novel potent payloads are used by ADCs, which allows researchers to exploit novel linkers to attach the antibody and payloads without disturbing their potency (Dragovich et al., 2018). Furthermore, some irrelevant antigen-target ADCs also may exert toxicity to tumor cells due to the vascular gap of tumors relative to the normal tissues, which is big enough to make ADCs penetrate into tumor cells (Cardillo et al., 2011), indicating the specific recognition of ADCs by tumor tissues on another aspect. Some prodrug strategies also are used in ADCs design, which modified the toxic payloads to inactive prodrugs, then utilized self-immolation groups and took advantage of the intratumoral environment to reduce the prodrugs to prototype drugs to exert intrinsic activity (Pei et al., 2018). Moreover, nanoparticles combining with the strategy of ACD prodrugs could also increase the activity and circumvent MDR (Qi et al., 2017). The key issues of ADCs are optimization of the appropriate antibody, the choice of proper antigen, the selection of high-activity cytotoxic payloads, stable linkage technology and optimization of DAR in future development. These strategies w...
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