A new monoclonal antibody is approved for the treatment of advanced colon cancer

Approved

On Feb 12th, 2004, the US Food and Drug Administration (FDA) approved a new monoclonal antibody called Cetuximab (Erbitux, formally known as C225, ImClone Systems and Bristol-Myers Squibb Company) for second line treatment of refractory colon cancer.

Cetuximab

Cetuximab is a chimeric monoclonal antibody (Mab) specific for the epidermal growth factor receptor (EGFR). EGFR's are receptors that span the cell membrane with ends protruding into both the outside and the inside of the cell. The part of the receptor that is found on the outside of the cell is called the extracellular domain and the end inside the cell is called the intracellular domain. Receptors are proteins that function to transmit signals from the outside of the cell to the cell nucleus found in the heart of the cell. A variety of proteins found in the blood stream may pass by the extracellular domain of the receptor, some may recognize it, and a smaller fraction will bind to it. Binding to the receptor initiates a variety of signals within the cell by way of the intracellular domain, including those commanding cell division, growth, and differentiation. These signals are transmitted only in the event that the receptor is activated by the appropriate protein. If something interferes with the binding, these signals will not be transmitted and the cell will not divide or grow. Over-expression of EGFR on the surface of many solid tumor cancer cells is very common. Studies have shown that increased expression of this receptor correlates with a poor prognosis and decreased survival.

Cetuximab is a man-made antibody that is specific for the EGFR. Cetuximab binds to the EGFR and thereby interferes with the normal, physiologic binding and cellular signaling pathways are interrupted. Put in a different way, by binding to the EGFR, Cetuximab does not allow the natural blood born protein to bind to the receptor and to transmit its signals for growth, cell division, and differentiation. When these signals are absent, the cell stops growing and will eventually die. Some believe that by overexpressing EGFR on their surface, tumors get multiple signals to grow and divide and therefore grow at a much faster rate than normal healthy tissue. Cetuximab blocks this growth signal and thereby kills the cancer cells.

Chimeric monoclonal antibodies

Monoclonal antibodies are antibodies made in large quantities in a laboratory that are all targeted at the same specific target. Chimeric refers to the fact that the antibody produced is a hybrid between a human and a mouse antibody. By using another species such as a mouse, laboratory researchers are able to produce multiple copies of a particular antibody. Since there is a possibility that a human will react to a mouse antibody, the mouse portion is minimized by hybridizing it to a human antibody.

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