Table 1.
ADCs approved by the FDA.
| ADC (Other Names, Commercial Name) | Target (Isotype Immunoglobulin) |
Payload (Mechanism of Action) | Linker | Indication (Year of FDA Approval) | Company |
|---|---|---|---|---|---|
| Gemtuzumab ozogamicin (GO, Mylotarg®) |
CD33 (IgG4) | Calicheamicin γ1 (CAL, cytotoxic antibiotic, DNA damage) | Cleavable hydrazone linker | Acute myeloid leukemia (AML) (2000–2010, 2017) | Pfizer (New York, U.S.) |
| Brentuximab vedotin (BV, SGN-35, Adcetris®) |
CD30 (cAC10 chimeric IgG1) |
Monomethyl auristatin E (MMAE, inhibition of microtubule polymerization) |
Protease-cleavable linker, maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl linker | Relapsed/refractory Hodgkin lymphoma and anaplastic large cell lymphoma (2011) | Seattle Genetics/Takeda(Washington, U.S./Tokyo, Japan) |
| Ado-trastuzumab emtansine (T-DM1, Kadcyla®) |
HER2 (IgG1) | Mertansine (DM1, inhibition of microtubule polymerization) | Non-cleavable thioether linker | HER2+ metastatic breast cancer (2013) Adjuvant treatment of patients with HER2+ early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab based treatment (2019) |
Roche (Basel, Switzerland) |
| Inotuzumab ozogamicin (INO, CMC-544, Besponsa®) |
CD22 (IgG4) | Calicheamicin derivative (CAL, cytotoxic antibiotic, DNA damage) |
Cleavable hydrazone linker | Acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) (2017) | Pfizer (New York, U.S.) |
| Moxetumomab pasudotox (CAT-8015, Lumoxiti®) | CD22 (Fv portion of the mAb) | PE38, a 38 kDa fragment of Pseudomonas exotoxin A (inhibition of protein synthesis) | Payload fused to the antibody using a cleavable amino acid linker | Relapsed or refractory hairy cell leukemia (HCL) (2018) | AstraZeneca (Cambridge, UK) |
| Trastuzumab deruxtecan (T-DXd, DS-8201a, Enhertu®) |
HER2 (IgG1) | Deruxtecan (DXd, topoisomerase I targeting) |
Enzymatically cleavable maleimide glycynglycynphenylalanyn-glycyn peptide linker | HER2+ metastatic breast cancer (2019) HER2+ locally advanced or metastatic gastric cancer (2021) |
AstraZeneca/Daiichi Sankyo (Cambridge, UK/ Tokyo, Japan) |
| Polatuzumab vedotin-piiq (PV, DCDS4501A, RG7596, Polivy®) | CD79b (IgG1) | Monomethyl auristatin E (MMAE, inhibition of microtubule polymerization) |
Protease-cleavable maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl linker | Diffuse large B-cell lymphoma (2019) | Roche (Basel, Switzerland) |
| Enfortumab vedotin (EV, ASG-22ME, AGS-22M6E, Padcev®) | Nectin 4 (IgG1) | Monomethyl auristatin E (MMAE, inhibition of microtubule polymerization) |
Cleavable maleimidocaproylvaline-citrulline linker | Locally advanced or metastatic urothelial cancer (2019) | Seattle Genetics/Astellas (Washington, U.S./Tokyo, Japan) |
| Sacituzumab govitecan (SG, IMMU-132, Trodelby®) | TROP-2 (IgG1) | SN-38 (topoisomerase I targeting) | Cleavable ydrolysable Ph sensitive CL2A linker | Metastatic Triple Negative Breast Cancer (2020) |
Immunomedics (New Jersey, U.S.) |
| Belantamab mafodotin (GSK2857916, Blenrep®) | BCMA, CD269 (IgG1) | Monomethyl auristatin F (MMAF, inhibition of microtubule polymerization) |
Non-cleavable maleimidocaproyl linker |
Relapsed and refractory multiple myeloma (2020) | GlaxoSmithKline (Brentford, UK) |
| Loncastuximab tesirine (ADCT-402, Zynlonta®) |
CD19 | Pyrrolobenzodiazepine (PBD) dimer toxin or SG3199 (DNA damage) | Valine-alanine cleavable, maleimide type linker | Relapsed or refractory large B-cell lymphoma (2021) | ADC Therapeutics S.A. (Lausanne, Switzerland) |