Antibody Drug Conjugate (ADC) is a complex formed by linking cytotoxic drugs to tumor-targeting monoclonal antibodies. It combines the characteristics of targeted drugs and chemotherapy drugs to achieve precise treatment. The concept of ADC drugs was proposed as early as 1900, but remained theoretical for a long time due to technical limitations. From 1990 to 2000, monoclonal antibodies gained widespread clinical use, lowering the barrier to ADC drug development.
There are two main ways for ADC to exert anti-tumor activity: one is that specific mAb binds to targeted cell surface antigens, is internalized by tumor cells and processed by endolysosomal system, and the payload is released into the cytoplasm, and finally induces apoptosis through cytotoxic pathway; the other is to induce tumor cell death through bystander killing effect.
FDA Approved Antibody Drug Conjugates
Since the first approval of Gemtuzumab ozogamicin in 2000, ADCs have accelerated into the global market after a slow start. At present, there are some ADC drugs approved for marketing in the world, seven of which target six different antigens -CD33, CD30, CD22, CD79b, B-cell maturation antigen (BCMA/TNFRSF17) and CD19-for hematologic malignancies. The other eight targeted solid tumors, targeting six different antigens -HER2, Nectin-4, tumor-associated calcium signal transducer 2 (TROP2), tissue factor (TF), EGFR, and folate receptor alpha (FRα).
| ADC Drug | Trade Name | Company | Target | Average DAR | Payload/Payload Class/Payload Action | mAb | Linker | Approval Year | Indication |
| Gemtuzumab ozogamicin | Mylotarg | Pfizer/Wyeth | CD33 | 2-3(Lys) | Ozogamicin/ calicheamicin/ DNA cleavage | IgG4 | AcBut acyhydrazone-disulfide (acid cleavable) | 2017;2000 | relapsed acute myelogenous leukemia (AML) |
| Brentuximab vedotin | Adcetris | Seagen Genetics, Millennium/Takeda | CD30 | 4(Lys) | MMAE/ auristatin/ microtubule inhibitor | IgG1 | Valine-citrulline (enzyme cleavable) | 2011 | relapsed HL and relapsed sALCL |
| Trastuzumab emtansine | Kadcyla | Genentech, Roche | HER2 | 3.5(Lys) | DM1/ maytansinoid/ microtubule inhibitor | IgG1 | SMCC (non-cleavable linker) | 2013 | HER2-positive metastatic breast cancer (mBC) following treatment with trastuzumab and a maytansinoid |
| Inotuzumab ozogamicin | Besponsa | Pfizer/Wyeth | CD22 | 2-3(Lys) | ozogamicin/ calicheamicin/ DNA cleavage | IgG4 | AcBut acyhydrazone-disulfide (acid cleavable) | 2017 | relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia |
| Polatuzumab vedotin-piiq | Polivy | Genentech, Roche | CD79 | 3-4(Cys) | MMAE/ auristatin/ microtubule inhibitor | IgG1 | Valine-citrulline (enzyme cleavable linker) | 2019 | relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) |
| Enfortumab vedotin | Padcev | Astellas/Seagen Genetics | Nectin4 | 4(Cys) | MMAE/ auristatin/ microtubule inhibitor | IgG1 | Valine-citrulline (enzyme cleavable) | 2019 | adult patients with locally advanced or metastatic urothelial cancer who have received a PD-1 or PD-L1 inhibitor, and a Pt-containing therapy |
| Trastuzumab deruxtecan | Enhertu | AstraZeneca/Daiichi Sankyo | HER2 | 8(Cys) | DXd/ camptothecin/ TOP1 inhibitor | IgG1 | Glycine-glycine-phenylalanine-glycine (enzyme cleavable) | 2019 | adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens |
| Sacituzumab govitecan | Trodelvy | Immunomedics | TROP2 | 7.6(Cys) | SN-38/ camptothecin/ TOP1 inhibitor | IgG1 | CL2A (acid cleavable) | 2020 | adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for patients with relapsed or refractory metastatic disease |
| Belantamab mafodotin-blmf | Blenrep | GlaxoSmithKline (GSK) | BCMA | 4(Cys) | MMAF/ auristatin/ microtubule inhibitor | IgG1 | Mc (non-cleavable) | 2020 | adult patients with relapsed or refractory multiple myeloma |
| Tisotumab vedotin-tftv | Tivdak | Seagen Inc | Tissue factor | 4(Cys) | MMAE/ auristatin/ microtubule inhibitor | IgG1 | Valine-citrulline (enzyme cleavable) | 2021 | Recurrent or metastatic cervical cancer |
| Loncastuximab tesirine-lpyl | Zynlonta | ADC Therapeutics | CD19 | 2.3(Cys) | SG3199/ PBD dimer/ DNA cleavage | IgG1 | Valine-citrulline (enzyme cleavable) | 2021 | Large B-cell lymphoma |
| Mirvetuximab soravtansine | Elahere | ImmunoGen | FRα | 3.3-5(Cys) | Maytansinoid DM4/ Folate receptor alpha | IgG1 | Sulfo-SPDB (cleavable) | 2022 | Platinum-Resistant Ovarian Cancer |
| Trastuzumab duocarmazine | SYD985 | Byondis | HER2 | 2.8(Cys) | Duocarmycin/ Seco-DUBA | IgG1 | Valine-citrulline (enzyme cleavable) | 2023 | Oncology |
Related ADCs Payloads at BOC Sciences
| Name | CAT | MW |
| MMAE | B0084-463280 | 717.98 |
| Auristatin T | 1799603-53-4 | 699.92 |
| Calicheamicin | B0084-470810 | 1368.35 |
| DM4 | B0238-477049 | 780.37 |
| Mertansine | B0238-474087 | 738.29 |
| Maytansinoid B | 1628543-40-7 | 735.26 |
| DM1-SMe | B0238-477047 | 784.38 |
| DXD | B2692-333861 | 493.48 |
| MMAF | B0238-464290 | 731.48 |
| PBD dimer | B0238-477053 | 725.79 |
| SG3199 | 1595275-71-0 | 584.66 |
| Duocarmycin DM | 577.98 | |
| Seco-DUBA | 1227961-59-2 | 526.97 |
Related ADCs Linkers at BOC Sciences
| Name | CAT | MW |
| N-Succinimidyl 4-(N-maleimidomethyl) trans-cyclohexane 1-carboxylate | 71875-81-5 | 334.32 |
| NH2-PEG4-GGFG-NH-CH2-O-CH2COOH | 2914227-54-4 | 670.71 |
| MCC | BADC-01506 | 236.27 |
| Val-Cit | BADC-00969 | 274.32 |
| Sulfo-SMCC sodium | B2699-079694 | 436.37 |
| SMCC | B2696-096388 | 334.32 |
| Fmoc-Val-Cit-PAB-PNP | B0238-477074 | 766.79 |
| Fmoc-Val-Cit-PAB | B0238-474627 | 601.704 |
| Mc-Val-Cit-PABC-PNP | B0238-464302 | 737.76 |
| Boc-Val-Cit-PAB-PNP | B2696-334034 | 644.7 |