Volume 18 Number 2 Fall 2001


Stronger and gentler

Radioimmunotherapy couples a radioactive molecule with a type of protein, known as an antibody, that sticks to cancer cells. When the antibody sticks to its target, the associated radiation kills the cancer cell and the cells in the immediate vicinity. Although the technique has proven very promising for the treatment of patients with non-Hodgkin’s B-cell lymphoma, Susan Knox, MD, PhD, and other Stanford researchers are now seeking to take radioimmunotherapy one step further.

“We’re aiming for greater efficacy without increasing toxicity,” says Knox, associate professor of radiation oncology. Knox is experimenting with a technique called pre-targeting, which breaks the therapy down into two discrete steps: antibody binding and irradiation of the cancer cell.

In pre-targeting, the researchers craft two separate structures that fit together like jigsaw puzzle pieces. One is attached to an antibody or other small molecule that will recognize and stick to the cancer cells. Its mate is attached to the radioactive molecule. The researchers inject the cancer-specific piece first and give it plenty of time to find and bind to its target. After giving the unbound molecules time to be excreted by the body — about 48 hours — the researchers then add the second piece that latches onto its partner and begins killing the associated cancer cells.

One of the benefits of pre-targeting is that it speeds up elimination of the unbound radioactive molecules from the patient’s blood. That’s because the radioactive molecule used in pre-targeting is much smaller than the radioactive molecule used in the standard protocol, and less prone to nonspecific entanglements with other molecules in the body. As a result, pre-targeting reduces the amount of time that non-cancerous tissue is irradiated.

Because pre-targeting reduces the radiation exposure of the normal tissue, the researchers can deliver a higher overall radiation dose to the cancer cells while keeping adverse side effects to a relatively minimal and acceptable level.

Related Stories:

The hunt is on

Assessing radioimmunotherapy

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Copyright © 2001, Stanford University School of Medicine. All rights reserved.