What Are Antibody-Drug Conjugates?

Antibody-drug conjugates (ADCs) are a class of targeted cancer therapies that have gained increasing importance in cancer management. Here are some key points about the use of ADCs in cancer treatment:

1. Mechanism of action:

– ADCs combine a monoclonal antibody that targets a specific tumour antigen with a potent cytotoxic drug or payload.

– The antibody binds to the target antigen on the tumour cell, and the drug is then internalized, leading to the selective killing of the cancer cell.

2. Target selection:

– The target antigen chosen for an ADC must be expressed on the surface of tumour cells but not (or minimally) on normal cells.

– Common targets include HER2, CD30, CD22, TROP2, and others that are overexpressed in various cancer types.

3. Payload selection:

– The cytotoxic drug or payload attached to the antibody is typically a highly potent compound, such as auristatins or maytansinoids.

– These payloads are designed to be more effective and less prone to drug resistance as compared to conventional chemotherapies.

4. Clinical applications:

– ADCs have been approved for the treatment of various haematological malignancies and solid tumours, including:

– Breast cancer (e.g., trastuzumab emtansine)

– Lymphoma (e.g., brentuximab vedotin)

– Acute lymphoblastic leukaemia (e.g., inotuzumab ozogamicin)

– Urothelial carcinoma (e.g., enfortumab vedotin)

5. Advantages:

– ADCs offer the potential for improved efficacy and reduced systemic toxicity compared to conventional chemotherapy.

– They can overcome drug resistance mechanisms by delivering high concentrations of cytotoxic agents directly to the tumour cells.

– ADCs can also be used in combination with other cancer therapies, such as immunotherapy or targeted agents.

6. Challenges:

– Careful selection of the target antigen and the cytotoxic payload is crucial to achieve the desired therapeutic index.

– Issues related to drug-linker stability, bystander effects, and the development of resistance can still occur.

– Ongoing research is focused on improving the design and conjugation strategies of ADCs to enhance their therapeutic potential.

Overall, ADCs represent a promising and rapidly evolving class of cancer therapeutics that leverage the specificity of monoclonal antibodies to selectively deliver potent cytotoxic agents to tumour cells.