Antibody–Drug Conjugates

A guided missile: an antibody that flies a chemo warhead straight to the tumor.

An ADC has three parts. The antibody finds a protein on the tumor surface. The payload is a cytotoxin far too potent to give on its own. The linker holds them together in the blood and releases the payload inside (or beside) the cancer cell. Payloads-per-antibody is the DAR.

The variables decide everything. Cleavable linkers release a membrane-permeable payload that also kills neighbouring cells (the bystander effect) — the trick behind Enhertu working even in low-target tumors. Payload class (topoisomerase-I vs auristatin vs maytansinoid vs PBD) sets the potency-vs-tolerability trade. Value concentrates in three choices: target, payload, linker.

How it works in depth

An antibody-drug conjugate has three engineered parts: a monoclonal antibody that recognizes a protein over-expressed on tumor cells (for example HER2, TROP2, Nectin-4 or folate receptor alpha), a cytotoxic payload far too toxic to give as free chemotherapy, and a chemical linker joining the two. The antibody circulates, binds its target antigen, and the cell internalizes the complex; the linker then releases the payload inside the cell to kill it. Two design choices dominate modern ADCs. The first is the drug-to-antibody ratio (DAR), the average number of payload molecules per antibody. The second is the bystander effect: with a membrane-permeable payload, drug released from one antigen-positive cell can diffuse into neighboring antigen-low cells, which helps in heterogeneous solid tumors. Payload chemistry has shifted notably. Earlier ADCs leaned on tubulin inhibitors (MMAE, DM1), but the current generation increasingly uses topoisomerase I inhibitors such as deruxtecan; reportedly nearly half of ADCs in Phase 3 now use a TOP1 payload.

Where the field is in 2025-2026

ADCs are one of oncology's hottest modalities. Roughly 15 are FDA-approved, and the class reportedly generated on the order of $13 billion in 2025 sales, with double-digit projected growth toward the end of the decade. Two new ADCs reached approval in 2025: datopotamab deruxtecan (Dato-DXd), cleared in HR-positive/HER2-negative metastatic breast cancer, and telisotuzumab vedotin. The central debates concern resistance (tumors losing antigen or upregulating drug efflux), tolerability (interstitial lung disease with deruxtecan agents, ocular and neuropathy effects), and how to sequence or combine ADCs. A major frontier is combinations—ADCs paired with checkpoint inhibitors or bispecifics—and bispecific ADCs that target two antigens to counter heterogeneity.

Leading programs & players

The commercial leaders include Enhertu (trastuzumab deruxtecan, Daiichi Sankyo/AstraZeneca), the category's top seller; Adcetris, Padcev and Tivdak (Pfizer, via its ~$43B Seagen acquisition completed in 2023-2024); Trodelvy (Gilead); Polivy (Roche); and Elahere (AbbVie, via its ~$10B ImmunoGen acquisition completed in 2024). Dealmaking remains intense: AstraZeneca's collaborations with Daiichi Sankyo span Enhertu, Dato-DXd and ifinatamab deruxtecan, while Merck partnered with China's Kelun-Biotech (whose sac-TMT/TROP2 ADC has reported Phase 3 lung-cancer wins). As of 2026, players such as GSK (B7-H3 ADCs) and Summit Therapeutics are pursuing ADC-plus-bispecific combinations.

FAQ

What is an antibody-drug conjugate (ADC)?

An ADC is a cancer drug that links a tumor-targeting antibody to a potent cytotoxic payload via a chemical linker, delivering chemotherapy selectively to cancer cells while sparing most healthy tissue.

What are the most successful ADC drugs?

Top approved ADCs include Enhertu (HER2), Trodelvy (TROP2), Padcev (Nectin-4), Adcetris (CD30), Polivy (CD79b) and Elahere (folate receptor alpha). Enhertu is the leading seller, reportedly around $3.75 billion in 2025.

What is the bystander effect in ADCs?

When an ADC's payload is membrane-permeable, drug released inside a targeted cell can diffuse into nearby cancer cells that express little or no antigen, helping treat tumors with uneven target expression.

What are next-generation ADCs?

Newer ADCs favor topoisomerase I inhibitor payloads (like deruxtecan), refined drug-to-antibody ratios, and bispecific designs that target two antigens at once, alongside combinations with checkpoint inhibitors to improve efficacy and overcome resistance.

Companies working on Antibody–Drug Conjugates

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