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Coming full circle to beat cancer

Medicine@Yale, 2013 - November


Working to curb a fatal cancer, and building on a precursor’s work

Richard L. Edelson, M.D., describes the workings of the immune system as “a huge, complex symphony.” Though not a musician, Edelson, chair and the Aaron B. and Marguerite R. Lerner Professor of Dermatology, has a conductor’s appreciation for the harmonious way the body mounts immune responses to cancer, and the discord that results when these attempts fail.

Edelson’s efforts to translate basic research into clinical practice have not only clarified how the immune system’s crucial sentinels, T cells, work, but have also helped transform cutaneous T cell lymphoma (CTCL), once a devastatingly fatal disease, into one that now rarely claims patients’ lives.

The cancer, which first appears as a simple rash and then spreads from the skin to other organs, used to have a median survival of only five years. Now, due to early diagnosis and new treatments, including a technique developed by Edelson, more than 98 percent of patients survive. Coincidentally, the path to an effective treatment began at Yale School of Medicine (YSM) when the late Aaron B. Lerner, M.D., Ph.D., discovered that the naturally occurring chemical 8-MOP was a potent chemotherapeutic. As a member of YSM’s Class of 1970, Edelson didn’t work with Lerner, but their paths are remarkably intertwined.

After an internship in internal medicine at the University of Chicago’s Pritzker School of Medicine, Edelson began a fellowship at the National Institutes of Health (NIH), and was there in 1972, the year human T cells were discovered. At the NIH, Edelson found that a group of seemingly disparate diseases were actually all T cell cancers. “The entity was renamed cutaneous T cell lymphoma. That’s when my career began,” he says.

Before 1972, doctors encountering CTCL knew they were dealing with a white blood cell cancer, but they didn’t know the cell type, or how malignant cells evolved from normal cells. Following the identification of T cells, an understanding of T cell biology and CTCL improved in parallel, and Edelson’s research over the years clarified the links between CTCL and the immune system.

In 1982, as a professor of dermatology at Columbia University’s College of Physicians and Surgeons, Edelson and colleagues made a new discovery. 8-MOP was known to be effective for psoriasis patients after being activated by ultraviolet (UV) light. After giving CTCL patients 8-MOP and passing their blood through a machine that zapped malignant cells with UV light, Edelson’s team found that the light-exposed cells effectively became an anti-cancer vaccine. “In the first patient we treated, the disease disappeared,” he says. The team later concluded that the treatment had immunized patients against the cancer.

The light treatment, called extracorporeal photochemotherapy (ECP), became the first FDA-approved cancer immunotherapy in 1988. ECP is now used around the world, not only to treat CTCL, but also in cases of organ transplant rejection and graft-versus-host disease following bone marrow transplants. The advance also introduced a new therapeutic principle: “The immune system is important in initial protection from that cancer, but by the time cancer is clinically evident, the immune system has been silenced,” Edelson says.

With Edelson’s return to YSM in 1986 to succeed Lerner as chair of the Department of Dermatology, the CTCL success story had come full circle. YSM remains a major center for ECP therapy, as well as research on how UV triggers the immune system. “At Yale, we train doctors to be clinicians who are dynamically involved in pushing their fields forward,” Edelson says. “That’s the kind of doctor I try to be.”

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