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

Eva Ellebaek, Trine Z. Iversen, Niels Junker, Marco Donia, Lotte Engell-Noerregaard, Özcan Met, Lisbet R. Hölmich, Rikke Sick Andersen, Sine Reker Hadrup, Mads Hald Andersen, Per thor Straten, Inge M. Svane

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalJournal of Translational Medicine
Volume10
Issue number1
Pages (from-to)169
Number of pages1
ISSN1479-5876
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Biochemistry, Genetics and Molecular Biology (all)
  • Medicine (all)
  • Adoptive cell therapy
  • Low-dose Interleukin-2
  • Malignant melanoma
  • Tumor infiltrating lymphocytes
  • aciclovir
  • antihistaminic agent
  • aprepitant
  • cyclophosphamide
  • domperidone
  • fluconazole
  • fludarabine phosphate
  • interleukin 2
  • palonosetron
  • pantoprazole
  • recombinant interleukin 2
  • sodium
  • sulfamethoxazole
  • trimethoprim
  • adoptive cell therapy
  • adoptive transfer
  • adult
  • aged
  • alopecia
  • anemia
  • article
  • autologous tumor infiltrating lymphocyte
  • blood cell count
  • blood transfusion
  • cancer growth
  • cancer regression
  • cell therapy
  • central nervous system metastasis
  • chemotherapy induced emesis
  • chill
  • clinical article
  • clinical trial
  • dermatitis
  • diarrhea
  • drug hypersensitivity
  • drug response
  • fatigue
  • feasibility study
  • female
  • fever
  • gastrointestinal symptom
  • human
  • hypertension
  • infection
  • leukopenia
  • low drug dose
  • lymphocytopenia
  • male
  • melanoma metastasis
  • nausea
  • neutropenia
  • peripheral lymphocyte
  • pilot study
  • side effect
  • T cell depletion
  • tachycardia
  • thrombocyte transfusion
  • thrombocytopenia
  • tumor associated leukocyte
  • vomiting
  • Adolescent
  • Adoptive Transfer
  • Adult
  • Aged
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-2
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating
  • Melanoma
  • Middle Aged
  • Neoplasm Metastasis
  • Pilot Projects
  • Young Adult
  • CELLULAR therapy

Cite this

Ellebaek, E., Iversen, T. Z., Junker, N., Donia, M., Engell-Noerregaard, L., Met, Ö., Hölmich, L. R., Andersen, R. S., Hadrup, S. R., Andersen, M. H., thor Straten, P., & Svane, I. M. (2012). Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. Journal of Translational Medicine, 10(1), 169. https://doi.org/10.1186/1479-5876-10-169