Table 1 Antibody drug conjugate (ADC) characteristics: linker class, payload and payload mechanism of action, drug antibody ratio (DAR), potency of the payload and of the ADC (IC50, nM) expressed as a range in sensitive and non-sensitive cell lines and ratio of IC50 ADC/payload in sensitive cells only
ADC | Linker | Payload | Type of payload | DAR | IC50 range payload, nM | IC50 range ADC, nM | IC50 ration ADC/payload-sensitive cell lines |
|---|---|---|---|---|---|---|---|
Belantamab mafodotin (Bienrep) | Non-cleavable linkers | MMAF, Auristatin | Tubulin polymerization promoters | 4 | 100–200 | – | |
Brentuximab vedotin (Adcetris) | Cathepsin B-sensitive linker | MMAE, Auristatin | Tubulin polymerization promoters | 4 | 0.07–3.1 | 0.003 − 0.125 | 0.042 (24 × more potent) |
Enfortumab vedotin (Padcev) | Cathepsin B-sensitive linker | MMAE, Auristatin | Tubulin polymerization promoters | 3.8 | 0.07–3.1 | 0.008–0.28 | 0.11 (9 × more potent) |
Gemtuzumab ozogamicin (Mylotarg) | Hydrazone linker/pH-sensitive linker | Ozogamicin, Calicheamicin | DNA double-strand breaking | 2–3 | 0.01–0.06 | 0.003—0.084 | 0.3 (3 × more potent) |
Inotuzumab ozogamicin (Besponsa) | Disulfide linker/glutathione-sensitive linker | Ozogamicin, Calicheamicin | DNA double-strand breaking | 6 | 0.01–0.06 | 0.009–0.43 | 0.9 (as potent as the payload) |
Loncastuximab tesirine (Zynlonta) | Cathepsin B-sensitive linker | SG3199, PBD dimer | DNA crosslinking | 2–3 | 0.15–1 | 0.002—0.0036 | 0.013 (77 × more potent) |
Mirvetuximab soravtansine (Elahere) | Disulfide linker/glutathione sensitive linker | DM4, Maytansinoid | Tubulin polimerization blockers | 3.5 | 0.03–0.06 | 0.5—24 | 16 × less potent |
Polatuzumab vedotin (Polivy) | Cathepsin B-sensitive linker | MMAE, Auristatin | Tubulin polymerization promoters | 3.5 | 0.07–3.1 | 0.07 | 1 (as potent as the payload) |
Sacituzumab govitecan (Trodelvy) | Hydrazone linker/pH-sensitive linker | SN-38, Topoisomerase inhibitor | DNA intercalation | 7.6 | 13–700 | 0.2- 0.3 | 0.015 (66 × more potent) |
Tisotumab vedotin (Tivdak) | Cathepsin B-sensitive linker | MMAE, Auristatin | Tubulin polymerization promoters | 4 | 0.07–3.1 | 0.01–3.8 | 0.14 (7 × more potent) |
Trastuzumab Deruxtecan (Enhertu) | Cathepsin B-sensitive linker | DXd, Topoisomerase inhibitor | DNA intercalation | 8 | 1.7–9.0 | 0.04—0.16 | 0.023 (43 × more potent) |
Trastuzumab Emtansine (Kadcyla) | Non-cleavable linker | DMl, Maytansinoid | Tubulin polimerization blockers | 3.5 | 0.79–7.2 | 0.2—29 | 0.25 (4 × more potent) |