Adoptive cell therapy for melanoma patients using tumor-infiltrating lymphocytes, lymphodepleting chemotherapy, and low-dose interleukin-2.

Abstract

2574 Background: Adoptive T cell therapy is based on isolation of tumor infiltrating lymphocytes (TIL) from autologous tumor, in vitro activation and expansion, and the reinfusion of these cells into a lymphodepleted patient. Together with high-dose interleukin (IL)-2 this treatment has in a few other countries successively been given to patients with advanced malignant melanoma and an impressive 50% response rate has been observed. Here we report the experience from a Danish Translational Research Center using low-dose subcutaneous IL-2 injections. Methods: A pilot trial including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease, and no CNS involvement. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of low-dose IL-2, 2 MIU/day. Results: Low-dose IL-2 considerably decreased the toxicity of the treatment with no grade 3-4 events related to this drug. Two of the 6 treated patients have an ongoing complete response (30+ and 7+ months), 2 patients had stable disease (4.5 and 5 months) and 2 patients progressed shortly after treatment. Five patients went through surgery but were not treated because of rapid disease progression (2), development of brain metastases (2) or the inability to grow cells (1). Tumor-reactivity of the infused cells and peripheral monocytes before and after therapy were analyzed. High tumor responses in the infusion products were correlated to clinical response and also an induction of tumor reactive T cells were seen in the peripheral blood for 1 patient in complete response. Conclusions: Complete and durable responses are induced after treatment with adoptive cell transfer in combination with low-dose IL-2 questioning the need for high and toxic doses of IL-2.