Antibody-drug conjugates(ADCs) are use specific linkers to connect antibodies and small molecule cytotoxic drugs, and their main components include antibodies, linkers and small molecular cytotoxic drugs. Antibody molecules mainly play the role of targeted delivery, and small molecule drugs play the role of effect. However, some antibodies also have anti-tumor pharmacodynamic effects.
Compared with other chemotherapeutic drugs, ADC drugs greatly improve the specificity of drug administration through the specific combination of antigen and antibody. The antibody binds to the specific antigen on the tumor cell membrane, induces endocytosis, and makes the antibody and the cytotoxicity attached to it The small molecule enters the cell, and then undergoes lysosome degradation. The small molecule drug is released into the cell and induces apoptosis through DNA insertion or inhibition of microtubule synthesis.
Antibody-drug conjugates(ADCs) are an important class of highly potent biopharmaceutical drugs designed as a targeted therapy for the treatment of people with cancer. As the hottest research topic, ADC technology is intended to target and kill only the cancer cells and spare healthy cells. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are examples of bioconjugates and immunoconjugates.
It has been more than 100 years since the concept of ADC was proposed, but there are still few varieties on the market and most of the varieties under research are still in the early stage. The main reason is that the development of ADC drugs is difficult and the technical barriers are high. ADC drugs need to go through multiple steps to take effect after entering the body, and each step has technical difficulties that need to be overcome.
As of November 2022, the FDA has approved 13 different ADCs, including Lumoxiti (moxetumomab pasudotox-tdfk), which we consider an immunotoxin.
The listing of Antibody-drug conjugates(ADCs) Approved by FDA:
| ADC Drug | Trade name | Maker | Disease Indication | Payload/Payload Class | Payload Action | Target | mAb | Linker | DAR | Approval Year |
| Mirvetuximab soravtansine | ELAHERE | ImmunoGen | Platinum-Resistant Ovarian Cancer | Maytansinoid DM4 | Folate receptor alpha | FRα | IgG1 | / | N/A | 2022 |
| Tisotumab vedotin-tftv | Tivdak | Seagen Inc | Recurrent or metastatic cervical cancer | MMAE/auristatin | microtubule inhibitor | Tissue factor | IgG1 | enzyme cleavable | 4 | 2021 |
| Loncastuximab tesirine-lpyl | Zynlonta | ADC Therapeutics | Large B-cell lymphoma | SG3199/PBD dimer | DNA cleavage | CD19 | IgG1 | enzyme cleavable | SG3199/PBD dimer | 2021 |
| Belantamab mafodotin-blmf | Blenrep | GlaxoSmithKline (GSK) | adult patients with relapsed or refractory multiple myeloma | MMAF/auristatin | microtubule inhibitor | BCMA | IgG1 | non-cleavable | 4 | 2020, withdrawn on 22 Nov. 2022 |
| Sacituzumab govitecan | Trodelvy | Immunomedics | 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 | SN-38/camptothecin | TOP1 inhibitor | TROP2 | IgG1 | acid cleavable | 7.6 | 2020 |
| Trastuzumab deruxtecan | Enhertu | AstraZeneca/Daiichi Sankyo | adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens | DXd/camptothecin | TOP1 inhibitor | HER2 | IgG1 | enzyme cleavable | 8 | 2019 |
| Enfortumab vedotin | Padcev | Astellas/Seagen Genetics | adult patients with locally advanced or metastatic urothelial cancer who have received a PD-1 or PD-L1 inhibitor, and a Pt-containing therapy | MMAE/auristatin | microtubule inhibitor | Nectin4 | IgG1 | enzyme cleavable | 3.8 | 2019 |
| Polatuzumab vedotin-piiq | Polivy | Genentech, Roche | relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) | MMAE/auristatin | microtubule inhibitor | CD79 | IgG1 | enzyme cleavable | 3.5 | 2019 |
| Moxetumomab pasudotox | Lumoxiti | Astrazeneca | adults with relapsed or refractory hairy cell leukemia (HCL) | PE38 (Pseudotox) | / | CD22 | IgG1 | Cleavable | N/A | 2018 |
| Inotuzumab ozogamicin | Besponsa | Pfizer/Wyeth | relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia | ozogamicin/calicheamicin | DNA cleavage | CD22 | IgG4 | acid cleavable | 6 | 2017 |
| Trastuzumab emtansine | Kadcyla | Genentech, Roche | HER2-positive metastatic breast cancer (mBC) following treatment with trastuzumab and a maytansinoid | DM1/maytansinoid | microtubule inhibitor | HER2 | IgG1 | non-cleavable | 3.5 | 2013 |
| Brentuximab vedotin | Adcetris | Seagen Genetics, Millennium/Takeda | relapsed HL and relapsed sALCL | MMAE/auristatin | microtubule inhibitor | CD30 | IgG1 | enzyme cleavable | 4 | 2011 |
| Gemtuzumab ozogamicin | Mylotarg | Pfizer/Wyeth | relapsed acute myelogenous leukemia (AML) | ozogamicin/calicheamicin | DNA cleavage | CD33 | IgG4 | acid cleavable | 2–3 | 2017; 2000 |
A stable link between the antibody and the cytotoxic (anti-cancer) agent is a crucial aspect of an ADC conjugation. A highly stable ADC linker will ensure that less of the cytotoxic payload falls off in circulation, driving an improved safety profile, and will also ensure that more of the payload arrives at the cancer cell, driving enhanced efficacy. Linkers are based on chemical motifs including disulfides, hydrazones or peptides (cleavable), or thioethers (noncleavable) and control the distribution and delivery of the cytotoxic agent to the target cell.
AxisPharm develops a broad range of Linkers and provide custom linker synthesis. Our current product catalog covers click chemistry tools such as DBCO, Tetrazine, TCO, BCN and Cycloprpene etc., biotin linkers, PEG linkers, peptide linkers, glucuronide linkers, photo cleavable linkers, Fluorescent Dye probe linkers and folic acid peg linkers. AxisPharm provides the most comprehensive linker and payloads for conjugation research.
As a customer-oriented contract research company, we offer flexible ADC Linker product kits and Bioconjugation services with competitive price.
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