A drug-to-antibody ratio (DAR) represents the average number of drug molecules conjugated to an antibody. This is an important attribute of antibody–drug conjugates (ADCs), which are complex molecules composed of an antibody linked to a biologically-active, cytotoxic (anticancer) drug. The DAR value of a drug can affect its efficacy. Low drug loading can reduce drug potency, while high drug loading can negatively affect the pharmacokinetics and toxicity of a drug. With current conjugation chemistry techniques—that is, lysine side-chain amidation or cysteine inter-chain disulfide bond reduction—a drug load of 0 to 8 drug molecules (D0 to D8) per antibody is commonly observed.
In the intact mass analysis workflow, BioPharma Finder application can calculate the drug load value for each component and the average DAR value for the entire experiment, as well as for each raw data file loaded for an experiment.
To calculate the DAR value for your intact mass analysis experiment, select the Enable Drug-to-Antibody Ratio checkbox on the Parameters > Identification page of the processing method editing wizard. On the Identification page, select a variable modification candidate for the DAR calculation from the drop-down list.
See Edit the Identification page and Use real-time optimization (RTO) to reprocess results.
When you select a drug linker from this list, after the application finishes target sequence matching, it automatically searches for modifications that match the selected drug linker.
After you process your experiment, the Average DAR pane on the Process and Review page displays the calculated average drug-to-antibody ratio (DAR) values using all of the components that have a drug load identification. See View the average drug-to-antibody ratio (DAR) values.