Table 1:

Important considerations in antibody–drug conjugate design

	Description	Importance
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