Table Info

Table 1.

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

Declarations

Author contributions

SM, SP and HKG contributed to the drafting and editing of the manuscript. SM created the figures. HKG contributed to conception and design of the review. All authors contributed to manuscript revision, read, and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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