Science Article
Hutch scientists have demonstrated that melanoma-fighting T cells can be transfused into patients, where the cells find their way to tumor sites for the deadly skin cancer.
The researchers also observed that such T cells react with normal skin cells, providing an explanation for an inflammatory reaction observed in melanoma patients treated with immunotherapy.
Dr. Cassian Yee, of the Clinical Research Division, evaluated the response of a patient with advanced melanoma to treatment with adoptive T-cell therapy, a technique which involves transfusing a patient with immune cells - T-lymphocytes - that can recognize a protein marker on the surface of melanoma cells.
Others involved in the study included Hutch investigators Drs. Phil Greenberg and Stanley Riddell and University of Washington researchers Drs. David Byrd, and John Thompson.
Featured as the cover story of the Dec. 4 edition of the Journal of Experimental Medicine, the study demonstrated that transfused T cells can persist in the body after infusion and localize to tumor sites, where they work to destroy cancerous cells.
"These results show that T cells can migrate to sites where tumor-specific proteins are expressed, and the cells are physiologically active," Yee said.
In addition, Yee observed areas of the patient's skin away from tumor sites that had decreased pigmentation - due to loss of melanin - accompanied by inflammation.
Melanoma patients treated with various types of immunotherapies - which stimulate an immune response directed at the tumor - often develop loss of skin pigmentation in sites away from the tumor. Scientists have speculated that this complication, which is not life-threatening and usually resolves itself in a matter of days, is due to an immune response against normal skin cells.
After analyzing the areas of inflammation in one patient, Yee and colleagues found infused T cells localized to those non-cancerous sites, demonstrating that the inflammation likely results from an immune response triggered by the transfused immune cells.
Although the inflammatory reaction of normal cells is a toxicity of treatment, Yee pointed out that it has important implications for treating cancers in the earliest stages of metastasis, when the cancer spreads beyond the site of the primary tumor.
"If the T cells can migrate to normal skin cells, then they should be able to find micro-metastases as well," he said.
To develop T cells with specific melanoma-fighting properties, scientists identify T cells that react against a protein found at abnormal levels in cancer cells. In this study, T cells were selected that were reactive against a melanoma-associated protein called MART-1.
Because these T cells cells also reacted with normal skin cells, MART-1 also must be present on the surface of normal cells, although perhaps at lower levels, a situation that is likely to be similar for very small tumors that develop in new sites away from the primary tumor.
Adoptive T-cell therapies for treating cancer and diseases have been studied and developed by Greenberg, Riddell and their Hutch colleagues.
