Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

作者：Ellebaek Eva; Iversen Trine Zeeberg; Junker Niels; Donia Marco; Engell Noerregaard Lotte; Met Ozcan; Holmich Li**et Rosenkrantz; Andersen Rikke Sick; Hadrup Sine Reker; Andersen Mads Hald; Straten Per Thor; Svane Inge Marie^*

来源：Journal of Translational Medicine, 2012, 10(1): 169.

DOI：10.1186/1479-5876-10-169

• Adoptive cell therapy
• Tumor infiltrating lymphocytes
• Malignant melanoma
• Low-dose Interleukin-2

Background: Adoptive cell therapy may be based on isolation of tumor-specific T cells, e. g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. %26lt;br%26gt;Methods: This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS %26lt;= 1, age %26lt;70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. %26lt;br%26gt;Results: Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3-4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. %26lt;br%26gt;Conclusion: Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

• 出版日期2012-8-21