Antibody-drug conjugates

Antibody-drug conjugates (ADCs) are a class of biopharmaceuticals designed for targeted cancer therapy. They consist of an antibody linked to a biologically active drug or toxin. The antibody specifically binds to antigens present on the surface of cancer cells, delivering the cytotoxic drug directly to the tumor, thereby minimizing the impact on healthy cells. This targeted approach aims to enhance the efficacy of cancer treatment while reducing side effects associated with traditional chemotherapy.

Overview

Antibody-drug conjugates are composed of three main components:

• An antibody that specifically targets a unique protein or antigen expressed on the surface of cancer cells.
• A cytotoxic drug (also known as a payload) that is capable of killing cancer cells once delivered.
• A linker that connects the antibody to the drug, which is stable in the bloodstream but releases the drug inside the target cells.

The mechanism of action of ADCs involves several steps:

1. The ADC binds to its target antigen on the surface of a cancer cell.
2. The complex is internalized by the cell through endocytosis.
3. Once inside the cell, the linker is cleaved, releasing the cytotoxic drug.
4. The released drug induces cell death, thereby killing the cancer cell.

Development and Approval

The development of ADCs is a complex process that involves the identification of suitable targets, antibodies, cytotoxic drugs, and linkers. The design of the linker is particularly critical, as it must be stable enough to prevent premature release of the drug but also capable of releasing the drug once inside the cancer cell.

Several ADCs have been approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) for the treatment of various cancers. These include:

• Ado-trastuzumab emtansine (Kadcyla) for HER2-positive breast cancer
• Brentuximab vedotin (Adcetris) for Hodgkin lymphoma and systemic anaplastic large cell lymphoma
• Enfortumab vedotin (Padcev) for urothelial carcinoma

Challenges and Future Directions

Despite the success of some ADCs, the development of these therapies faces several challenges, including the identification of suitable targets that are highly expressed on cancer cells but not on healthy cells, managing off-target effects, and improving the therapeutic index of ADCs.

Future research in the field of ADCs is focused on discovering new targets, developing more potent and specific antibodies, improving linker chemistry, and identifying more effective cytotoxic drugs. Advances in these areas have the potential to make ADCs a more powerful tool in the fight against cancer.

See Also

• Monoclonal antibodies
• Chemotherapy
• Targeted therapy
• Pharmacokinetics