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January 13, 2014

The ABCs of monoclonal antibody drugs

Photo | contributed Madhavi Gorusu, oncologist and assistant clinical professor, University of Connecticut School of Medicine

In an interview with HBJ's Sujata Srinivasan, Madhavi Gorusu, an oncologist and assistant clinical professor at the University of Connecticut School of Medicine, explains the basics of monoclonal antibody drugs.

How does a monoclonal antibody drug treat cancer?

Antibodies are proteins that target specific antigens such as bacteria and viruses, which cause the immune system to produce antibodies against it. Antibodies attach to antigens and the process activates the body's immune system to destroy the cells containing the antigens. Our body naturally produces antibodies as part of the immune system's response to germs, vaccines, etc. Many copies of a specific antibody can be made in the lab, which can be engineered to target a specific antigen expressed by cancer cells.

Monoclonal antibodies are manufactured using a type of cell called hybridoma, engineered by fusing an antibody-producing immune cell called B cell to a tumor cell. Hybridoma then multiplies to produce a continuous supply of specific antibodies. When the monoclonal antibody attaches itself to the cancer cell, it marks the cancer cell and makes it easier for the immune system to find and destroy it.

To date, the FDA has approved at least 12 different monoclonal antibody treatments for cancer.

How effective and safe is it?

Monoclonal antibody treatment is different from traditional chemotherapy drugs in that they are targeted therapies, which selectively attach to cancer cells. This means better efficacy and relatively fewer side effects. On the other hand, traditional chemotherapy medications lack the ability to differentiate between normal cells and cancer cells. This results in several side effects. In certain combinations, monoclonal antibodies can be combined with chemotherapy or radiation to produce synergistic effects.

What is the role of Receptor Tyrosine Kinases (RTKs) in cancer?

RTKs are key elements of signal transduction pathways that mediate cell- to-cell communication. They are transmembrane receptors, which play an important role in cell growth. Certain RTKs are overexpressed and activated in many types of cancers and ultimately are one of the key pathways for tumor growth. One of the strategies to prevent this cell-to-cell communication and thereby prevent cancer cell growth is by using antibodies against RTKs.

What are some challenges with RTK inhibitors?

One of the challenges in the successful treatment with RTK inhibitors is development of drug resistance by patients.

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