| Autor: |
Liao MZ; Genentech Inc, South San Francisco, CA, USA., Leipold DD; Genentech Inc, South San Francisco, CA, USA., Chen SC; Zymeworks, Vancouver, BC, Canada., Li Z; Genentech Inc, South San Francisco, CA, USA., Kamath AV; Genentech Inc, South San Francisco, CA, USA., Li C; Genentech Inc, South San Francisco, CA, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Xenobiotica; the fate of foreign compounds in biological systems [Xenobiotica] 2024 Aug; Vol. 54 (8), pp. 543-551. Date of Electronic Publication: 2024 Sep 27. |
| DOI: |
10.1080/00498254.2024.2351044 |
| Abstrakt: |
ADCs represent a transformative class of medicine that combines the specificity of monoclonal antibodies with the potency of highly cytotoxic agents through linkers, aiming to enhance the therapeutic index of cytotoxic drugs. Given the complex molecular structures of ADCs, combining the molecular characteristics of small-molecule drugs and those of large-molecule biotherapeutics, there are several unique considerations when designing nonclinical-to-clinical PK/PD translation strategies.This complexity also demands a thorough understanding of the ADC's components - antibody, linker, and payload - to the overall toxicological, PK/PD, and efficacy profile. ADC development is a multidisciplinary endeavour requiring a strategic integration of nonclinical safety, pharmacology, and PK/PD modelling to translate from bench to bedside successfully.The ADC development underscores the necessity for a robust scientific foundation, leveraging advanced analytical and modelling tools to predict human responses and optimise therapeutic outcomes.This review aims to provide an ADC translational PK/PD framework by discussing unique aspects of ADC nonclinical to clinical PK translation, starting dose determination, and leveraging PK/PD modelling for human efficacious dose prediction and potential safety mitigation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
