Table 1.
Types of currently used ADC components
| Component | Type | Desired characteristics |
|---|---|---|
| Payloads | Microtubule inhibitors | Potent cytotoxic amenable to linking |
| • Auristatins (MMAE, MMAF) | ||
| • Maytansinoids (DM1, DM4) | ||
| DNA‐damaging agents | ||
| • Calicheamicin | ||
| • Ducaramycins | ||
| • Pyrrolobenzodiazepines (PBD) | ||
| RNA polymerase (alpha‐amanitin) | ||
| Linkers | Cleavable | Stable in circulation but released in tumor |
| • Protease cleavable e.g. valine‐citruline | ||
| • Acid labile e.g. hydrazone | ||
| • Disulfide linkers e.g. SPDB, SPP | ||
| Non‐cleavable (e.g. MCC) | ||
| Conjugation chemistry | Via lysine residues | Homogenous mixture, stable |
| Via cysteines derived from reduced interchain disulfides | ||
| Site specific conjugation | ||
| • Engineered cysteines | ||
| • Unnatural amino acids | ||
| • Enzymatic conjugation |