Experimental Therapy Beats Back One Patient's Melanoma

WEDNESDAY June 18, 2008 -- Patient "Number Four," taking part in an experimental melanoma treatment program at the Fred Hutchinson Cancer Research Center in Seattle, was a very lucky man.

After receiving an infusion of his own, fortified immune system T cells, the man's melanoma, which had already spread to a lung and to a lymph node in his groin and had not responded to other therapies, went into complete remission.

Researchers reporting in the June 19 issue of the New England Journal of Medicine say this is the first time a patient's cloned T cells used alone have put an advanced solid-tumor cancer into complete remission.

The man was followed for two years, at which time he was still in remission. Doctors lost track of him after that.

"No way would we say this is a cure but he had a complete response and, fortunately, for him, it lasted longer than just a few months or weeks," said study senior author Dr. Cassian Yee, an associate member at Hutchinson's clinical research division.

"I don't think this represents any standard of care, but I view it as shining a light on the direction in which we perhaps should be heading," said Dr. Louis M. Weiner, director of the Lombardi Comprehensive Cancer Center at Georgetown University, in Washington, D.C. "It's giving us some insights into what the necessary conditions are for an anti-cancer immune response to be effective."

Immunotherapy, which engages a patient's own immune system to fight cancer, is an emerging art and science. The method holds the promise of being much less toxic than other treatments, though recent research has pointed out that it may not be as safe as once hoped.

Research shows several instances when a patient's own immune system kicked in to oust a cancer even without help from sophisticated new technologies. Dr. Vijay Trisal, assistant professor of surgical oncology at City of Hope Cancer Center in Duarte, Calif., recounted two such cases: One, a woman whose melanoma had spread to her lungs, brain and other parts of her body, was stung by a bee and subsequently recovered not only from the bee sting but also from the cancer. Two, a man with advanced melanoma who stepped into a poison ivy patch and experienced a similar recovery.

Similar happenings have been recorded for other types of cancer.

"Maybe there were 10 cells in the body that were very good, sort of a smart bomb against the melanoma, but they weren't enough," Trisal explained. "The bee sting or poison ivy multiplied these smart bombs one thousand times so suddenly this army of 10 became an army of a billion."

And that is essentially what the authors of the new study did, collecting CD4+ T-cells from nine melanoma patients, isolating single cells that they believed would target a certain protein on the tumor cells, cultivating and enriching these cells, and then re-infusing them into the patient.

Patient Four, a 52-year-old man, received five billion cloned CD4+ T cells designed to go after the melanoma-associated NY-ESO-1 antigen. The new cells stayed in the patient's body for 80 days. Two months later, the man's melanoma was gone.

The man received a higher dose than the first three patients but the same or lower dose than the subsequent five patients. The first three had no response at all while the later patients saw some response, but none as dramatic as Patient Four.

"We don't know why he was the lucky one," Yee said. "Maybe it was something specific to him or his tumor. Maybe he had a low-level pre-existing response that we were able to augment."

And therein lies a major problem with immunotherapy as it exists now. "We know this works but it's a shot in the dark," Trisal said. "It works maybe in one in 100 people instead of one in 1,000 where the body itself fights the cancer."

The question is how to make the process more efficient and effective.

"Obviously there's a lot of promise for immunotherapy of this kind but I think that we're several years away from making this any kind of standard therapy," Yee said. At this point, the therapy needs to be standardized to the patient and it can take months to grow the required cells, during which time the patient's condition could deteriorate dramatically.

"It would be helpful to try to streamline the process," Yee said. "[Right now], we can only target a small fraction of patients. What we're looking for in the future is to streamline this process and decrease the time it takes to grow cells and to see if we can target other antigens. This is a proof of principle: Yes, we can use CD4+ clones."

More information

Visit the American Cancer Society for more on immunotherapy.

Posted: June 2008


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