Table 2.
USFDA approved ADCs along with their specific characteristics
| Sr. No | ADC (trade name/generic name) | Company, year of USFDA Approval | Antibody | Drug/Payload, MoA | Linker | Conjugation Method | DAR | Target Antigen | Indications |
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| 1. | Mylotarg® (Gemtuzumab ozogamicin) | Wyeth/Pfizer, 2000, withdrawn 2010; reapproved 2017 | Humanizid IgG4-kappa | Ozogamicin (N-acetyl-γ-calicheamicin 1,2-dimethyl hydrazine dichloride); DNA disrupting agent through binding to the minor groove in the DNA | Cleavable acyl hydrazone; pH and redox sensitive, bifunctional 4-(4 acetylphenoxy)butanoic acid linker | Lysine (Stochastic) | ~2–3 | CD33 | Acute Myeloid leukemia. |
| 2. | Adcetris® (Brentuximab vedotin) | Seagen/Takeda, 2011 | Chimeric IgG1 | Monomethyl auristatin E (MMAE, Vedotin); Microtubule disrupting agent | Cleavable Valine-citrulline |
Internal Cysteine (Stochastic) | ~4 | CD30 | Hogkin’s lymphoma, Anaplastic large cell lymphoma |
| 3. | Kadcyla® (ado-Trastuzumab emtansine) | Gentech/Roche, 2013 | Humanized IgG1 | DM1 (Maytansine derivative); Microtubule inhibitor | Non-cleavable thioether; N-maleimidomethyl cyclohexane-1-carboxylate (MCC) linker |
Lysine (Stochastic) | ~3.5 | HER2 | HER2 positive metastatic breast cancer |
| 4. | Besponsa® (Inotuzumab ozogamicin) | Wyeth/Pfizer, 2017 | Humanized IgG4-kappa | Ozogamicin (N-acetyl-γ-calicheamicin): DNA disrupting agent | Cleavable hydrazone; acid dependent 4-(4-acetylphenoxy) butanoic acid liker | Lysine (Stochastic) | ~6 | CD22 | Non-Hodgkin’s lymphoma, Acute lymphoid leukaemia |
| 5. | Lumoxit® (Moxetumumab pasudotox-tdfk) | Astrazeneca, 2018 | Anti-CD22 antibody | Pseudomonas Exotoxin 38 (PE38); Protein synthesis inhibition | Cleavable Fusion Protein (antibody and payload) | – | – | CD22 | Relapsed or refractory Hairy cell leukemia |
| 6. | Polivy® (Polatuzumab vedotin) | Genentech/Roche, 2019 | Humanized IgG1-kappa | Monomethyl auristatin E (MMAE); Microtubule disrupting agent | Cleavable Valine-citrulline; maleimidocaproyl-valyl-citrullinyl-p-aminobenzyloxycarbonyl (mc-val-cit-PABC) linker |
Internal Cysteine (Stochastic) | ~3.5 | CD79b | Relapsed or refractory Diffuse large B- cell lymphoma |
| 7. | Padcev® (Enfortumab vedotin) | Astellas Pharma/Seagen, 2019 | Humanized IgG1 | Monomethyl auristatin E (MMAE); Microtubule disrupting agent | Cleavable Valine-citrulline; maleimidocaproyl-valyl-citrullinyl-p-aminobenzyloxycarbonyl (mc-val-cit-PABC) type linker | Internal Cysteine (Stochastic) | ~4 | Nectin-4 | Metastatic urothelial/bladder cancer |
| 8. | Enhertu® (fam-Trastuzumab deruxtecan-nxki) | Daichi sankyo / AstraZeneca, 2019 | Humanized IgG1 | Deruxtecan/DXd (Exatecan/ Camptothecin derivative); Topoisomerase inhibitor |
Cleavable maleimide Tetrapeptide (Glycine-glycine-phenylalanine-glycine) linker |
Internal Cysteine (Site-Specific) | ~8 | HER-2 | HER2 positive Metastatic breast cancer |
| 9. | Trodelvy® (Sacituzumab govitecan-hziy) | Immunomedics, 2020 | Humanized IgG1-kappa | SN-38 (Active metabolite of Irinotecan); Topoisomeraseinhibitor | Cleavable Carbonate (CL2A) linker |
Internal Cysteine (Site-Specific) | ~7.6 | TROP2 (trophoblast cell surface antigen-2) | Triple negative breast cancer |
| 10. | Blenrep® (Belantamab mafodotin-blmf) | Glaxosmithkline/Seagen,2020 | Humanized IgG1 | Monomethyl auristatin F (MMAF); Microtubule inhibitor | Non-cleavable Maleimidocaproyl linker |
Internal Cysteine (Stochastic) | ~4 | B cell maturation antigen (BCMA) | Relapsed or Refractory multiple myeloma |
| 11. | Zynlonta® (Loncastuximab tesirine) | ADC therapeutics, 2021 | Chimeric IgG1 | Pyrrolobenzodiazepine (PBD) dimer SG3199; DNA minor groove binding | Cleavable Valine-alanine, maleimide type linker containing a spacer PEG (n = 8) |
Internal Cysteine (Stochastic) | ~2.8 | CD19 | B-cell non- Hodgkin lymphoma |
| 12. | Tivdak® (Tisotumab vedotin-tftv) | Seagen/ Genmab, 2021 | Humanized IgG1-kappa | Monomethyl auristatin E (MMAE); Microtubule inhibitor | Cleavable Valine-citrulline linker; maleimidocaproyl-valyl-citrullinylp-aminobenzyloxy carbonyl (mc-val-cit-PABC) type linker |
– | ~4 | Tissue factor (TF)-011 | Recurrent or metastatic cervical cancer |
| 13 | Elahere® (Mirvetuximab soravtansine-gynx) | Immunogen, 2022 | Humanized IgG1 | IMGN-853 (May-tansinoid DM4) Microtubule inhibitor |
Cleavable disulfide linker; N-Succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (Sulfo-SPDB) | – | ~3.5:1 | Folate receptor α (FRα) | FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer |