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Details: Let There Be Light
Twenty years ago, a photochemical experiment mysteriously cured two cancer patients. Now the riddle has been solved.
November/December
2003
by Bruce Fellman
In the early 1980s, Richard Edelson, a dermatologist and immune system biologist then at Columbia University, took a shot in the dark. Dermatologists had been alleviating psoriasis for years using light-box treatments in concert with methoxypsoralen (8-MOP), a chemical found in figs, limes, celery, and Queen Anne's Lace. No one knew why it worked. But in psoriasis, as in cancer, cell growth is in overdrive, so Edelson decided to try 8-MOP on patients with cutaneous T-cell lymphoma (CTCL), an often deadly malignancy.
Edelson invented a treatment in which he took some of the patient's blood, mixed it with 8-MOP, exposed it
to light, and reinfused it into the patient's body a few hours later. He called it photopheresis. "No one had ever shined light on blood and returned it to a patient," he recalls.
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"We're learning to read the language of the cells."
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The first study involved five patients, all of them near death. After a few months of treatment, two suddenly became cancer-free. Both remain so today. "It was a moment you never forget," says Edelson. "I was stunned."
Photopheresis is effective, though hardly perfect: about one quarter of CTCL patients experience a reduction in malignant cells of more than than 75 percent. It is now used in 150 university medical centers in the United States and Europe. Recently, Edelson and his Yale colleagues finally found out why it works.
Malignant cells, like stealth bombers within the body, evade the immune system's defenses by hiding the unique proteins, called antigens, that would identify them as invaders and stimulate T-cells to find and destroy them. But 8-MOP, light, and the physical process of photopheresis expose the malignant cells.
First, photoactivated 8-MOP and UV light damage the cancer cells in a patient's blood, leaving dying cells that are then engulfed by white blood cells. But in a miracle of serendipity, the process of withdrawing the blood stimulates ordinary white blood cells to metamorphose into immune-system messengers called dendritic cells. After digesting a cancer cell, a dendritic cell displays the cancer cell's antigens on its surface -- a red flag that calls down a T-cell attack.
Edelson and Yale scientists Carole Berger and Douglas Hanlon have now improved on photopheresis with a technique known as transimmunization. In it, the blood and 8-MOP mixture is forced through an extremely thin Plexiglas plate. This greatly increases the number of dendritic cells. After light is shined on the Plexiglas, the mixture is incubated for 24 hours. The additional time lets the dendritic cells mature and increases the chance that they will encounter the damaged cancer cells.
The blood mixture, full of primed dendritic cells, becomes a personalized cancer vaccine. Small wonder that the procedure is raising high hopes; Edelson has been swamped by calls from desperate cancer patients. He cautions that the therapy has not even been tested yet. (If his research protocols are approved, it will soon be used in trials against lung cancer and other solid tumors.) But he is hopeful. "Our knowledge of the immune system has come of age," he says. "We're learning to read the language of the cells. We anticipate substantial breakthroughs."  |
