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
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
The hunt is on