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Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates

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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

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