Antibody-drug conjugates represent one of the most significant pharmacological innovations in modern oncology. By combining the targeting precision of a monoclonal antibody with the cell-killing potency of cytotoxic chemotherapy, ADCs function as guided missiles that deliver their payload directly to cancer cells while limiting damage to healthy tissue. This approach has produced remarkable clinical results across an expanding range of tumor types.
Anatomy of an ADC
Every ADC consists of three components: the antibody (which recognizes a specific antigen on cancer cells), the linker (a chemical bridge that holds the drug to the antibody), and the payload (a cytotoxic agent far more potent than conventional chemotherapy). When the antibody binds its target on a cancer cell, the entire ADC is internalized through endocytosis. Inside the cell, the linker is cleaved, releasing the cytotoxic payload to destroy the cell from within.
The engineering of each component critically determines the ADC's therapeutic index. The antibody must bind a target that is highly expressed on cancer cells but minimally expressed on normal tissue. The linker must be stable enough in the bloodstream to prevent premature payload release (which would cause systemic toxicity) but efficiently cleaved once internalized by the cancer cell. The payload must be potent enough to kill cancer cells at the concentrations achieved after intracellular release — ADC payloads are typically 100 to 1,000 times more potent than conventional chemotherapy.
The Bystander Effect
A key mechanism that amplifies ADC efficacy is the bystander effect. After the payload is released inside a target-positive cell and kills it, some payload molecules can diffuse into neighboring cancer cells — including those that may not express the target antigen. This is particularly important for tumors with heterogeneous target expression. Trastuzumab deruxtecan (Enhertu) exemplifies this: its membrane-permeable payload enables bystander killing that contributes to its remarkable activity even in cancers with low HER2 expression that would not traditionally be classified as HER2-positive.
ADCs Transforming Cancer Treatment
Several ADCs have fundamentally changed treatment paradigms. Trastuzumab deruxtecan (Enhertu) has redefined HER2-targeted therapy in breast cancer and gastric cancer, showing efficacy even in HER2-low tumors previously considered HER2-negative. Enfortumab vedotin (Padcev), targeting Nectin-4, combined with pembrolizumab has become a new first-line standard for advanced bladder cancer, outperforming decades of platinum-based chemotherapy. Sacituzumab govitecan (Trodelvy) targets Trop-2 in triple-negative breast cancer and urothelial carcinoma.
In hematologic malignancies, ADCs have been equally transformative. Brentuximab vedotin (Adcetris) targeting CD30 changed the frontline treatment of Hodgkin lymphoma. Polatuzumab vedotin targeting CD79b improved outcomes in diffuse large B-cell lymphoma. Gemtuzumab ozogamicin targets CD33 in AML.
The Future of ADCs
The ADC pipeline is one of the most active areas in oncology drug development, with over 100 ADCs in clinical trials targeting diverse antigens across virtually every tumor type. Next-generation innovations include bispecific ADCs (targeting two antigens simultaneously), immune-stimulating ADC payloads (replacing cytotoxic drugs with immune agonists), and ADCs with novel linker chemistry for improved therapeutic windows. PipelineEvidence tracks all FDA-approved ADCs across our complete therapy database.