Creative Biolabs is professional in antibody-drug conjugates (ADCs) manufacture and analysis, and now provides ADME characterization service to help customers have a better understanding of the dynamic interactions between the biological system and ADC.
ADCs are designed to kill cancer cells in a target-dependent manner and the first step in this process is the monoclonal antibody component of an ADC selectively binds a cell-surface tumor antigen. Upon ADC binding, the entire ADC-antigen complex is internalized through receptor-mediated endocytosis. The ADC-antigen complex then traffics to lysosomal compartments and is degraded, releasing active cytotoxic drug inside the target cell. Free drug causes cancer cell death through either tubulin polymerization inhibition or DNA binding/damage depending on the drugs mechanism of action. ADME properties refer to the absorption, distribution, metabolism/catabolism, and excretion of ADCs in the biological system. Acquainting the ADME properties of your ADC candidates is essential to understand how they actually work and what attributes may be necessary for clinical success, in detail, ADME characterization can provide critical assessments in lead selection, optimization, and clinical development of your ADC candidates. Various antibodies, drugs and linkers can be used to assemble an ADC, resulting in a kind of complex molecules, due to which, there is no standard “one size fits all” ADME analysis approach can be applied to all ADCs. Experienced scientists from Creative Biolabs are committed to design and perform a custom ADME characterization protocol to meet each customer’s requirement.
The distribution of ADC should be similar to unconjugated antibody, which indicates that ADC deliver drug to the specific target. It can be affected by target antigen expression and internalization. Moreover, it can be assessed by measuring the radioactivity of labeled unconjugated antibody and ADC in plasma and tissues.
The catabolism and elimination processes are similar with that of mAbs. They are mediated mainly by either receptor-mediated endocytosis or ﬂuid-phase pinocytosis with subsequent trafficking to the lysosome, followed by enzymatic degradation. The difference between total-ADC concentrations and active-ADC concentrations reflects the ADC metabolism.
Knowing the elimination pathways of ADCs helps to determine the need for special patient population studies. In order to determine the rate and route of excretion, The ADC or unconjugated antibody is radiolabeled and administered to models and then the radioactivity in the excreta is measured.
ADME characterization for an ADC is a complex process and Creative Biolabs has great technical power and enriched expertise to accomplish the whole process and offers you a comprehensive ADME profile.