NCI Researchers Confirm the Effectiveness of Immunotherapy Approach to Treating Melanoma
A team of researchers, led by Steven A. Rosenberg, M.D., at the National Cancer Institute, part of the National Institutes of Health, have
found that patients with advanced melanoma who had not responded to previous therapies experienced a significant reduction in the size of their
cancers as a result of receiving a new immunotherapy. This immunotherapy consisted of a combination of chemotherapy and reintroduction of their
own (autologous) activated lymphocytes. Autologous lymphocytes are white blood cells that have been removed from the patient, activated or
re-educated to attack the tumor, then reintroduced into the patient. The promise of this therapy is that a patient's own immune system can be
used to effectively treat existing tumors. Results are reported in the April 2005 issue of the Journal of Clinical Oncology.*
"These results represent confirmation of our original findings that were published in Science in 2002," said Rosenberg. The findings
published in 2002** were in an initial patient population of 13 and these new findings represent almost a threefold increase in patient
numbers.
Thirty-five patients with melanoma that had progressed throughout the body were chosen for the study. The patients had not responded
successfully when treated with standard therapies and had developed growing tumors. Blood was drawn from the patients, and then lymphocytes, a
type of white blood cell in the blood that can attack tumors, were separated from other parts of the blood. Next, patients were treated for
two days with the chemotherapy agent cyclophosphamide followed by five days of fludarabine. The chemotherapy drugs were used to reduce the
number of lymphocytes circulating in the blood, therefore reducing competition for the newly activated tumor-fighting lymphocytes being
reintroduced in to the blood stream.
After the seven days of chemotherapy, the patients received their own lymphocytes that had been renewed with increased tumor-fighting
capacity. They also received a high dose of Interleukin-2 (IL-2), a protein made by the body that makes the tumor-fighting cells mature and
multiply.
Of the 35 patients in this study, 18 (51 percent) experienced an improvement in the amount of tumor present at diverse sites in the body:
lung, liver, lymph nodes, brain and skin. Eight other patients demonstrated a mixed or minor response. Of the 18 patients showing improvement,
15 had a partial response that lasted from two months to more than two years. It is noteworthy that there were three (9 percent) patients who
continued to experience complete disappearance of tumors. This result is particularly significant because these patients had not responded to
standard treatments or chemotherapies used in treating patients with melanoma.
Thirteen patients relapsed after positive response to therapy and developed tumors at pre-existing or new sites within the body. There were
no treatment-related deaths in this study. The loss of white blood cells, which fight infections, led to the development of infections in seven
patients. Toxicities related to the chemotherapy and administration of a high dose of IL-2 were easily managed.
The results of this study prove that a combination of chemotherapy and infusion of autologous, stimulated, white blood cells can have an
impact on metastatic melanoma tumors in patients who do not respond to other therapies. "The results of this study are encouraging, and
suggest that some patients with melanoma who do not respond to conventional treatments may get a durable benefit from treatments based on using
their own immune cells" said Mark Dudley, Ph.D., coauthor of the study.
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For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer
Information Service at 1-800-4-CANCER (1-800-422-6237).
* Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ,
Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer
therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastic melanoma. Journal
of Clinical Oncology. April 1, 2005;23(10).
** Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR,
Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in
patients after clonal repopulation with antitumor lymphocytes. Science 2002;298:850-854.
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