Antibody-Drug Conjugate — Targeted Chemotherapy

An antibody-drug conjugate is an engineered biopharmaceutical therapeutic composed of three distinct structural components: a monoclonal antibody, a cytotoxic payload, and a biochemical linker. The antibody component is designed to bind with high specificity to a particular tumour-associated antigen overexpressed on the malignant cell surface.

Once the antibody attaches to its target antigen, the entire conjugate is internalized by the cancer cell via receptor-mediated endocytosis. The complex travels to the lysosome, where enzymatic cleavage or acidic degradation breaks the chemical linker. This intracellular release liberates the potent cytotoxic agent—frequently a topoisomerase I inhibitor or microtubule-disrupting toxin—triggering cell cycle arrest and apoptosis while minimizing systemic cytotoxic exposure.

ADCs have transformed oncology by making exceptionally potent cytotoxic agents clinically usable. Compounds previously deemed far too toxic for traditional intravenous chemotherapy can now be delivered safely straight into tumours. For patients, this often means improved response rates, longer disease control, and a different side-effect profile compared to conventional systemic cytotoxic treatments.

Treatment with an ADC depends directly on biomarker testing to confirm that the patient's tumour expresses the specific target antigen. Pathologists perform immunohistochemistry or fluorescence in situ hybridization on tumour biopsy samples to evaluate markers such as HER2, Trop-2, Nectin-4, or CD30. Treatment is only offered if these targets are adequately present.

ADCs are widely used across multiple cancer types. They are standard treatments in HER2-positive and HER2-low breast cancer, metastatic urothelial (bladder) cancer, and non-small cell lung cancer. ADCs are also extensively used in haematological malignancies, including refractory Hodgkin and non-Hodgkin lymphomas, acute myeloid leukemia, and relapsed multiple myeloma.

Prescribing an ADC requires meticulous target verification and specific toxicity monitoring. Because the payloads are potent, ADCs can cause targeted adverse reactions; for example, certain agents carry risks of interstitial lung disease or pneumonitis, requiring baseline and routine high-resolution chest imaging. Others can induce peripheral neuropathy, ocular toxicities, or cytopenias depending on the payload and linker architecture.