Abstract
Purpose
This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy.
Methods
this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years.
Results
The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload.
Conclusion
These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales.
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Abbreviations
- ADC:
-
Antibody-drug conjugates
- ADCC:
-
Antibody-dependent cellular cytotoxicity
- CDC:
-
Complement-dependent cytotoxicity
- DM1:
-
N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)- maytansine
- EGFR:
-
Epidermal growth factor receptor
- FcRn:
-
Neonatal Fc receptor
- MMAE:
-
Monomethyl auristatin E
- MTD:
-
Maximum tolerated doses
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Xu, S. Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates. Pharm Res 32, 3577–3583 (2015). https://doi.org/10.1007/s11095-015-1729-8
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DOI: https://doi.org/10.1007/s11095-015-1729-8