ADC Drugs — Complete Guide to Antibody‑Drug Conjugates

Antibody‑Drug Conjugates (ADCs) are targeted cancer medicines that combine a monoclonal antibody specific for a tumor antigen with a potent cytotoxic payload via a chemical linker. The antibody directs the toxic payload to tumor cells, enabling delivery of high‑potency drugs with reduced systemic exposure.

Unlike traditional chemotherapy, ADCs are intended to target and kill only cancer cells while sparing healthy cells. Learn more about advanced cancer treatments.

1. Binding: ADC binds to a cell-surface antigen highly expressed on tumor cells.
2. Internalization: The ADC–antigen complex is internalized into the tumor cell (endocytosis).
3. Payload release: In lysosomes or by linker cleavage the payload is released and exerts cytotoxic effects (e.g. microtubule inhibition, DNA topoisomerase inhibition).
4. Cell death and bystander effect: Depending on the payload and linker, released drug may diffuse to adjacent tumor cells (bystander effect) or act only inside the targeted cell.

Key design elements: Antibody (target), Linker (cleavable vs non‑cleavable), and Payload (MMAE/MMAF, DM1/DM4, topoisomerase I inhibitors, calicheamicin, etc.).

• Advantages: targeted delivery, higher therapeutic index vs conventional chemo, potential for activity in refractory disease.
• Limitations: antigen heterogeneity, limited drug‑to‑antibody ratio (DAR), off‑tumor toxicity if antigen expressed on normal tissue, development of resistance mechanisms.

The table below shows representative FDA‑approved ADCs (selection). Replace or expand this list as new approvals appear.

*Dates reflect approximate period of regulatory activity — always verify current FDA/EMA approvals and labeling before clinical use.

When comparing ADCs pay attention to:

• Target antigen: expression level, tumor specificity and heterogeneity.
• Linker chemistry: cleavable linkers enable payload release inside lysosomes; non‑cleavable linkers rely on antibody degradation.
• Payload potency & class: microtubule inhibitors vs topoisomerase inhibitors vs DNA‑alkylating agents.
• Drug‑to‑antibody ratio (DAR): higher DAR increases potency but may affect pharmacokinetics and toxicity.

Ideal candidates for ADC therapy typically have tumors that:

• Express the ADC target at sufficient level (confirmed by IHC or molecular testing).
• Have progressed on standard therapies or are unsuitable for conventional chemotherapy.
• Have organ function compatible with the expected toxicity profile (liver, bone marrow, lung parameters).

Exclusion Criteria / Safety Flags

• Severe hepatic impairment or active uncontrolled infection.
• Severe baseline cytopenias (unless expected to recover).
• Pregnancy or breastfeeding.
• Known hypersensitivity to components of the ADC.

Hundreds of ADC programs are in clinical trials with innovations in bispecific antibodies, site‑specific conjugation, new payload classes (e.g. immune modulators), and combinations with checkpoint inhibitors or targeted small molecules.

Explore our technology transfer services to learn about the latest developments in ADC research and clinical applications.

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