Summary of the most clinically relevant ADCs in selected tumour types
| Tumour type(s) | ADC | Target antigen | Antibody | Linker | Payload | Features and approvals |
|---|---|---|---|---|---|---|
| GBM | Depatux-M/ABT-414 | EGFR | Humanized IgG1 | Non-cleavable MC linker | MMAF | Targets mutant EGFRvIII and tumours overexpressing wild-type EGFR [171] |
| GBM | AMG 595 | EGFR | Human IgG1 | Non-cleavable MCC linker | DM1 | Targets only EGFRvIII and not wild-type EGFR [98] |
| Gastric, CRC | T-DXd/DS-8201 | HER2 | Humanized IgG1 | Cleavable tetrapeptide-based linker | DXd (topoisomerase inhibitor/exatecan derivative) | High DAR of 8 (whilst maintaining stability), novel payload, effective across various histologies, bystander effect [172]. FDA breakthrough designation for GOJ cancer 2020 |
| CRC, UC | RC48 | HER2 | Humanized IgG1 (hertuzumab) | Cleavable MC- valyl-citrullinyl-p-aminobenzyloxycarbonyl (MC-val-cit-PABC) linker | MMAE | Higher antibody affinity for HER2, more potent ADCC, bystander effect [39] |
| CRC | T-DM1 | HER2 | Humanized IgG1 (trastuzumab) | Cleavable tetrapeptide based (MCC) linker | DM1 | First FDA approved ADC in solid organ tumours, vulnerable to drug efflux and resistance [173] |
| UC | SG | Trop-2 | Humanized IgG (hRS7) | Cleavable maleimide based linker (CL2A) | SN-38 (irinotecan metabolite) | High DAR of 7.6, rapid clearance reducing off target toxicity [174]. FDA accelerated approval for UC 2021 [174] |
| UC | EV | Nectin-4 | Humanized IgG1 (AGS-22M6) | Cleavable MC valine-citrulline linker | MMAE | FDA accelerated approval 2019 and breakthrough therapy designation with ICI in 2020 for la/mUC [58, 64, 175] |
| Prostate | PSMA ADC | PSMA | Human IgG1 | Cleavable MC valine-citrulline linker | MMAE | Future development unknown [73, 74] |
| Prostate | MEDI3726 | PSMA | Humanized IgG1 | Cleavable valine-alanine linker | PBD | Development discontinued [75, 176] |
ADCC: antibody-dependent cell-mediated cytotoxicity; MC: maleimidocaproyl; MCC: maleimidomethyl cyclohexane-1-carboxylate