Summary of the most clinically relevant ADCs in selected tumour types

Tumour type(s)ADCTarget antigenAntibodyLinkerPayloadFeatures and approvals
GBMDepatux-M/ABT-414EGFRHumanized IgG1Non-cleavable MC linkerMMAFTargets mutant EGFRvIII and tumours overexpressing wild-type EGFR [171]
GBMAMG 595EGFRHuman IgG1Non-cleavable MCC linkerDM1Targets only EGFRvIII and not wild-type EGFR [98]
Gastric, CRCT-DXd/DS-8201HER2Humanized IgG1Cleavable tetrapeptide-based linkerDXd (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, UCRC48HER2Humanized IgG1 (hertuzumab)Cleavable MC- valyl-citrullinyl-p-aminobenzyloxycarbonyl (MC-val-cit-PABC) linkerMMAEHigher antibody affinity for HER2, more potent ADCC, bystander effect [39]
CRCT-DM1HER2Humanized IgG1 (trastuzumab)Cleavable tetrapeptide based (MCC) linkerDM1First FDA approved ADC in solid organ tumours, vulnerable to drug efflux and resistance [173]
UCSGTrop-2Humanized 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]
UCEVNectin-4Humanized IgG1 (AGS-22M6)Cleavable MC valine-citrulline linkerMMAEFDA accelerated approval 2019 and breakthrough therapy designation with ICI in 2020 for la/mUC [58, 64, 175]
ProstatePSMA ADCPSMAHuman IgG1Cleavable MC valine-citrulline linkerMMAEFuture development unknown [73, 74]
ProstateMEDI3726PSMAHumanized IgG1Cleavable valine-alanine linkerPBDDevelopment discontinued [75, 176]

ADCC: antibody-dependent cell-mediated cytotoxicity; MC: maleimidocaproyl; MCC: maleimidomethyl cyclohexane-1-carboxylate