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T Cell Clones Shrink Melanoma Tumors

SEATTLE — Nov. 12, 2002 — The study, conducted by Dr. Cassian Yee, a researcher at the Fred Hutchinson Cancer Research Center, involved 10 people diagnosed with advanced melanoma. For each patient immune system cells able to identify and target melanoma were extracted and cloned. The cloned cells were expanded in the lab and re-injected into the patient. The results of the study showed that in five patients tumors stopped growing for up to one year and in three of the patients the tumors appeared to shrink.

"While we did not expect to cure the cancers, the technique appears to benefit patients by curbing the spread of their tumors," says Dr. Yee.

Below is an advisory distributed today by the Proceedings of the National Academy of Sciences (PNAS). The paper can be found in the online early edition of PNAS at www.pnas.org.

Soldier Clones: T Cells Target Tumors

A preliminary clinical trial suggests that armies of T cells generated in the lab can be injected into patients to halt the spread of cancerous tumors. One strategy for treating cancer is to sensitize the immune system to the presence of tumors so it can attack the cancerous cells. Vaccinating patients with proteins present on the cancerous cells could kick the immune system into action. Instead of relying on the immune system to manufacture a defense, however, Cassian Yee and colleagues tried supplying ready-made soldiers.

In the lab, the authors grew T cells, those cells that destroy invaders or aberrant cells. To insure that the T cells found their target, the authors trained them on their quarry, stimulating the cells with a protein found on metastatic melanoma cells. The authors then injected these designer T cells into 10 patients over the course of 12 weeks. The results, reported in article #6000, indicate that the T cells clones were able to home in on the tumors, which regressed slightly or stabilized in 8 of the 10 patients, for an average period of 11 months.

In addition to T cells, the injections contained IL-2, a chemical that stimulates the T cells to replicate, resupplying the troops. Although IL-2 can be toxic in high doses, the patients showed little reaction to the low dose of IL-2 used.

"Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastic melanoma: in vivo persistence, migration and anti-tumor effect of transferred T cells" by C. Yee, J.A. Thompson, D. Byrd, S.R. Riddell, P. Roche, E. Celis, P.D. Greenberg.

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Fred Hutchinson Cancer Research Center
The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson, in collaboration with its clinical and research partners, the University of Washington Academic Medical Center and Children's Hospital and Regional Medical Center, is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 38 nationwide. For more information, visit the center's Web site at www.fhcrc.org.