Target expression |
Tumour-specific antigen against which the antibody is directed |
Target should be expressed preferentially on tumour cells over non-malignant cells; high-level expression is advantageous, although not necessary |
Target internalisation |
Intracellular trafficking of the target antigen and the bound antibody-drug conjugate via receptor-mediated endocytosis |
Rate and extent of internalisation affects drug uptake and release in tumour and non-malignant cells |
Linker stability |
Covalent coupling of the cytotoxic drug to the antibody |
Stable linkers prevent premature release of cytotoxic drug to non-target tissue; to maximise drug exposure in tumour tissue and minimise toxic effects, drug release should happen intracellularly |
Conjugation |
Specific method of attachment of the cytotoxic drug and linker to the antibody |
The method of conjugation, number of drugs per antibody (drug: antibody ratio), and drug position have an effect on the physical properties of the antibody-drug conjugate, thereby affecting aggregation, antigen binding, and clearance of the conjugate from the circulation |
Cytotoxic payload |
Type of cytotoxic drug that is conjugated to the antibody |
The mechanism of action and potency of cytotoxic agents has implications in terms of frequency of dosing and toxic effects |