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

J Transl Med. 2012 Aug 21;10:169. doi: 10.1186/1479-5876-10-169.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adoptive Transfer*
  • Adult
  • Aged
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Pilot Projects
  • Young Adult

Substances

  • Interleukin-2

Associated data

  • ClinicalTrials.gov/NCT00937625