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Melanoma Patient Tumor Free in T-Cell Clone Study
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Immune Therapy for Late-Stage Melanoma: No More Cancer in 1 of 11 Patients
By Daniel J. DeNoon
Reviewed by Laura J. Martin, MD
March 5, 2012 -- One of 11 patients facing death from treatment-resistant, late-stage melanoma is cancer free 3.5 years after experimental treatment with clones of his own immune cells.
"The patient is doing fine. He is a teacher in high school, and has been teaching from two or three months after he finished therapy," study leader Cassian Yee, MD, of Seattle's Fred Hutchinson Cancer Research Center, tells WebMD.
Despite this dramatic result, the therapy this patient received isn't ready for prime time. Ten other study patients, who also had failed to benefit from multiple previous treatments, eventually died.
Successful treatment depended on isolating and cloning just the right kind of cancer-fighting immune cell. This happened in only two of the 11 study patients. Yee says his team now has refined the technique. Further clinical studies are under way.
The treatment is one of several forms of adoptive immunotherapy now under intense study at several medical centers. Each of these treatments captures a patient's own tumor-fighting cells, grows them to high numbers in the lab, and infuses them back into the patient.
National Cancer Institute researcher Steven Rosenberg, MD, PhD, pioneered the field. Rosenberg used immune cells taken from inside patients' melanoma tumors. A small number of patients treated with these tumor-infiltrating lymphocytes, or TIL, became cancer free.
But only selected patients have the right kind of TIL for this treatment. And there's another huge drawback. The treatment calls for patients to have their existing T cells wiped out by intensive chemotherapy, sometimes with whole-body radiation. And then they have to take high doses of an immunity-boosting drug, which also causes severe side effects.
"Unfortunately, this is fairly toxic and limits the availability of the treatment to patients who can handle the toxicity," Dana-Farber Cancer Institute researcher Marcus O. Butler, MD, tells WebMD. Butler, who has conducted similar research, reviewed the study findings for WebMD.
Butler says that Yee's team showed that anti-tumor immune cells can survive when patients are given much less toxic chemotherapy and lower doses of the immune-boosting drugs.
Melanoma Treatment 'Renaissance'
That's not the end of the story. Researchers are also combining their adoptive immunotherapy regimens with other types of immune therapies.
One of these treatments, Yervoy, was recently approved by the FDA. Yervoy is a man-made antibody that attacks melanoma tumors.
By combining adoptive immunotherapy with Yervoy, the researchers hope to deliver a potent one-two punch to late-stage melanoma, no matter how extensively the cancer has spread through the body.
For example, only about 16% of patients respond to Yervoy treatment alone. But when Butler's team gave Yervoy to patients who had already received adoptive immunotherapy, they had more success: Three of five patients had partial tumor remission and two others had stable disease.
"Among investigators, we agree almost certainly that immune therapy is going to work when we combine different agents," says Butler, soon to become an assistant professor at the University of Toronto.
Yee says that although adoptive immunotherapy studies began with melanoma patients, the treatment should work for other types of cancer.
"We are starting to look at ovarian cancer and sarcoma," Yee says.
While adoptive immunotherapy remains on the drawing board, Yee and Butler encourage patients to enroll in clinical trials.
"There are more options for melanoma now than ever before," Yee says. "But if patients volunteer for reasonable clinical trials, we think patients can move science forward faster. We are grateful to the patients who are brave enough to explore this new frontier. This is almost like a renaissance period for immunotherapy."
Yee's study appears in the March 5 early online edition of the Proceedings of the National Academy of Science. Butler's study appeared in the April 27, 2011, issue of Science Translational Medicine.
SOURCES: Cassian Yee, MD, clinical researcher, Fred Hutchinson Cancer Research Center and professor of medical oncology, University of Washington School of Medicine.Marcus O. Butler, MD, instructor, Dana-Farber Cancer Institute and Harvard Medical School; assistant professor, University of Toronto.Chapuis, A.G. Proceedings of the National Academy of Science, published online March 5, 2012.Butler, M.O. Science Translational Medicine, April 27, 2011.News release, Fred Hutchinson Cancer Research Center.Robert, C. Chapman, P.B. New England Journal of Medicine, June 30, 2011.Chapman, P.B. New England Journal of Medicine, June 30, 2011.Ernstoff, M.S. Chapman, P.B. New England Journal of Medicine, June 30, 2011.Rosenberg, S.A. Clinical Cancer Research, July 1, 2011.Goff, S.L. Journal of Immunotherapy, October 2010.Dudley, M.E. Clinical Cancer Research, Dec. 15, 2010.