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

Journal of Translational Medicine

Inge Marie Svane¹  Per thor Straten³  Mads Hald Andersen³  Sine Reker Hadrup³  Rikke Sick Andersen³  Lisbet Rosenkrantz Hölmich²  Özcan Met¹  Lotte Engell-Noerregaard¹  Marco Donia⁴  Niels Junker¹  Trine Zeeberg Iversen¹  Eva Ellebaek¹ 

[1] Department of Oncology, Copenhagen University Hospital, Herlev, Denmark;Department of Plastic Surgery, Copenhagen University Hospital, Herlev, Denmark;CCIT, Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital, Herlev, Denmark;Department of Biomedical Sciences, University of Catania, Catania, Italy

关键词: Low-dose Interleukin-2;    Malignant melanoma;    Tumor infiltrating lymphocytes;    Adoptive cell therapy;   

Others  :  1205912
DOI  :  10.1186/1479-5876-10-169

 received in 2012-05-02, accepted in 2012-08-14,  发布年份 2012

【 摘 要 】

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.

Methods

This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <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.

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.

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.

【 授权许可】

   
2012 Ellebaek et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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