The quest for effective systemic therapy for metastatic melanoma has taken researchers down diverse paths ranging from cytotoxic chemotherapy, to immunotherapy, to ‘targeted’ therapy. Initial clinical studies utilizing many of these agents have frequently appeared quite promising, thus each has been embraced successively with enthusiasm. Unfortunately, despite improved disease-free survival in some patients, durable responses to most of these agents remain dismally rare.

However, a significant glimmer of hope has derived from the observation that durable responses can be obtained with interleukin-2 in a small but significant subset of patients. This has prompted extensive research aimed at harnessing the power of T cells for melanoma immunotherapy. In this issue of The Melanoma Letter, Dr. Steven Rosenberg of NCI shares with us his innovative treatment method of adoptive cell transfer, which entails harvesting a melanoma patient’s own tumor-infiltrating lymphocytes (TIL) and isolating the cells expressing T cell receptors that can recognize melanoma-specific antigens. These cells are grown in large numbers and re-injected into the patient with the goal of targeting the patient’s melanoma cells.

In an accompanying article, Drs. Jedd Wolchok and Stephanie Terzulli present another potentially more generalizable approach to harnessing T cells for melanoma therapy. They describe their experience with the use of antibodies to CTLA-4 in the treatment of advanced melanoma. By preventing T cell inhibition, anti-CTLA-4 therapy unleashes the immune system to permit more robust T cell activity against melanoma.

In addition to yielding ‘cures’ for some patients, these therapies are providing significant insights into the interplay of different subsets of T cells, which will hopefully lead to more effective, generalizable, and safe therapies for advanced melanoma.