Antibody–Drug Conjugates (ADCs) are a class of targeted cancer therapies composed of a potent cytotoxic payload chemically linked to a monoclonal antibody (mAb) via a specialized chemical linker. This design enables the precise delivery of the drug to tumor cells, helping to minimize systemic toxicity and enhance treatment efficacy.
The history of ADC development began with the first clinical trial in 1983, in which an anti-carcinoembryonic antigen antibody conjugated to vindesine was tested in patients with advanced metastatic carcinomas. In 2000, the U.S. FDA approved gemtuzumab ozogamicin (Mylotarg) as the first ADC on the market, targeting CD33-positive acute myeloid leukemia. As of April 2025, the U.S. FDA has approved 13 ADC drugs for the treatment of various hematologic malignancies and solid tumors (see Table below).
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ADC Name and Maker |
Payload |
Linker |
Disease |
Target Antigen |
Approval year |
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Datopotamab deruxtecan Datroway® (Daiichi Sankyo and AstraZeneca)
|
Deruxtecan |
MC-Gly-Gly-Phe-Gly |
HR+/HER2− metastatic breast cancer |
Trop-2 |
2025 |
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Mirvetuximab soravtansine Elahere® (Abbvie) |
DM4 |
Sulfo-SPDB |
Platinum-resistant ovarian cancer |
Folate receptor α |
2022 |
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Tisotumab vedotin Tivdak® (Genmab/Seagen)
|
MMAE |
MC-Val-cit-PAB |
Recurrent/metastatic cervical cancer |
Tissue factor |
2021 |
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Loncastuximab tesirine Zynlonta® (ADC Therapeutics)
|
PBD dimer |
Mal-Amide-PEG8-val-cit-PAB |
Large B-cell lymphoma |
SG3199/CD19 |
2021 |
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Belantamab mafodotin Blenrep® (GSK) |
MMAF |
Non-cleavable |
relapsed and refractory multiple myeloma |
BCMA |
2020 |
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Sacituzumab govitecan Trodelvy® (Gilead) |
SN-38 |
CL2A |
Triple-negative breast cancer (TNBC), HR+/HER2− breast cancer |
Trop 2 |
2020 |
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Trastuzumab deruxtecan Enhertu® (AstraZeneca and Daiichi Sankyo) |
Deruxtecan (DXd) |
MC-Gly-Gly-Phe-Gly |
HER2-positive breast, gastric, and lung cancers |
HER2 |
2019 |
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Enfortumab vedotin Padcev® (Genmab/Seagen)
|
MMAE |
MC-Val-cit-PAB |
Urothelial cancer |
Nectin-4 |
2019 |
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Polatuzumab vedotin Polivy® (Genetech/Roche) |
MMAE |
MC-Val-cit-PAB |
diffuse large B-cell lymphoma |
CD79 |
2019 |
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Inotuzumab ozogamicin Besponsa® (Pfizer)
|
Calicheamicin |
Acid-labile (hydrazone) |
Relapsed/refractory B-cell precursor acute lymphoblastic leukemia |
CD22 |
2017 |
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Trastuzumab emtansine Kadcyla® (Roche)
|
DM1 |
Non-cleavable MCC |
HER2-positive breastcancer |
HER2 |
2013 |
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Brentuximab vedotin Adcetris®
|
MMAE |
MC-Val-cit-PAB |
relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma |
CD30 |
2011 |
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Gemtuzumab ozogamicin Mylotarg® |
Calicheamicin |
Acid-labile (hydrazone) |
Acute myeloid leukemia |
CD33 |
2000 (reapprove 2017) |
Among the key components of ADCs, the linker plays a pivotal role not only in attaching the payload to the antibody, but also in determining the stability in circulation, drug release profile, and overall therapeutic index. Advances in linker chemistry—such as cleavable vs. non-cleavable designs, site-specific conjugation strategies, and hydrophilic masking groups—have been instrumental in overcoming early challenges related to toxicity and efficacy, and continue to drive innovation in the next-generation ADC platforms.
As a leading bioconjugation linker supplier, Precise PEG offers a comprehensive portfolio of customized and off-the-shelf ADC linkers to support cutting-edge therapeutic development and translational research.
References:
1. Food and Drug Administration Website. Drugs@FDA: FDA-Approved Drugs. Accessed April 2025.
2. ADC Database (ADCdb). https://adcdb.idrblab.net/. Accessed April 2025.