Linkers with shielding effect yield higher success rates for Antibody Drug Conjugates
Minimizing ADC aggregation through linker shielding to maximize ADC functionality & happiness
Antibody drug conjugates (ADCs) are composed of three main components – the antibody, the linker and the payload or cytotoxic drug. Linkers are the key liaison connecting the antibody to the drug. However, linkers play a far bigger role in ADC design & development as well as the resultant functionality. One of the key ADC development and functionality criteria influenced by linkers is the percentage of aggregate formation and the resultant ADC solubility
Cytotoxic drugs or payloads are often hydrophobic compounds rendering themselves unsuitable to high solubility, due to the tendency to attract similar moieties and become “sticky”. When such drugs are conjugated to an antibody through linkers which cannot provide shielding to the hydrophobic nature of payloads, multiple ADCs constructs stick to each other. This leads to aggregate formation and lower solubility.
However, with the right linkers such as dPEG based – branched, SideWinder and BodyArmor linkers, which provide the required hydrophilicity and shielding,there is decrease in the propensity of the ADCs to aggregate, thereby increasing their solubility. This video shows the difference between ADCs with and without the shielding effect from linkers – leading to varying levels of happiness co-efficient.
Check out the linkers providing the much-required shielding:
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