Antibody-drug conjugate

Antibody-drug conjugate (ADC) is a targeted cancer therapy that combines an antibody with a biologically active drug or cytotoxin. This combination allows for the selective delivery of the drug to cancer cells, thereby minimizing the impact on healthy cells and reducing side effects.

Structure and Mechanism

An ADC consists of three main components:

1. The antibody: A monoclonal antibody that specifically targets a tumor-associated antigen.
2. The linker: A chemical bridge that connects the antibody to the drug. The linker is designed to be stable in the bloodstream but release the drug once inside the target cell.
3. The cytotoxin: A potent drug that can kill cancer cells. Common cytotoxins used in ADCs include auristatins, maytansinoids, and calicheamicins.

The mechanism of action involves the binding of the ADC to the target antigen on the surface of the cancer cell. After binding, the ADC is internalized into the cell, where the linker is cleaved, releasing the cytotoxin to exert its cytotoxic effects.

Development and Approval

The development of ADCs involves several stages, including preclinical research, clinical trials, and regulatory approval. The first ADC to receive FDA approval was gemtuzumab ozogamicin in 2000 for the treatment of acute myeloid leukemia.

Clinical Applications

ADCs are primarily used in the treatment of various types of cancer, including:

• Breast cancer
• Lymphoma
• Leukemia
• Lung cancer

Advantages and Challenges

Advantages

• Targeted delivery of cytotoxins to cancer cells
• Reduced systemic toxicity
• Potential for combination with other therapies

Challenges

• Development of resistance
• Complexity of manufacturing
• High cost of treatment

Future Directions

Research is ongoing to improve the efficacy and safety of ADCs. Innovations include the development of new linkers, more potent cytotoxins, and antibodies with higher specificity.

See Also

• Monoclonal antibody therapy
• Targeted therapy
• Chemotherapy
• Immunotherapy