Cancer Immunology, Immunotherapy

, Volume 61, Issue 10, pp 1791–1804

Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide: results from a phase II trial

  • Eva Ellebaek
  • Lotte Engell-Noerregaard
  • Trine Zeeberg Iversen
  • Thomas Moerch Froesig
  • Shamaila Munir
  • Sine Reker Hadrup
  • Mads Hald Andersen
  • Inge Marie Svane
Original article

Abstract

Dendritic cells (DC) are the most potent antigen presenting cells and have proven effective in stimulation of specific immune responses in vivo. Competing immune inhibition could limit the clinical efficacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibitor have been added to a DC vaccine with the intend to dampen immunosuppressive mechanisms. Twenty-eight patients with progressive metastatic melanoma were treated with autologous DCs pulsed with survivin, hTERT, and p53-derived peptides (HLA-A2+) or tumor lysate (HLA-A2). Concomitantly the patients were treated with IL-2, Cyclophosphamide, and Celecoxib. The treatment was safe and tolerable. Sixteen patients (57 %) achieved stable disease (SD) at 1st evaluation and 8 patients had prolonged SD (7–13.7 months). The median OS was 9.4 months. Patients with SD had an OS of 10.5 months while patients with progressive disease (PD) had an OS of 6.0 months (p = 0.048) even though there were no differences in prognostic factors between the two groups. Despite the use of metronomic Cyclophosphamide, regulatory T cells did not decrease during treatment. Indirect IFN-γ ELISPOT assays showed a general increase in immune responses from baseline to the time of 4th vaccination. Induction of antigen-specific immune responses was seen in 9 out of 15 screened HLA-A2+ patients. In conclusion, the number of patients obtaining SD more than doubled and 6-month survival significantly increased compared to a previous trial without Cyclophosphamide and Celecoxib. A general increase in immune responses against the tested peptides was observed.

Keywords

Malignant melanoma Dendritic cell vaccination Immunotherapy Metronomic cyclophosphamide 

Supplementary material

262_2012_1242_MOESM1_ESM.pdf (168 kb)
Supplementary material 1 (PDF 168 kb)

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Eva Ellebaek
    • 1
    • 2
  • Lotte Engell-Noerregaard
    • 1
    • 2
  • Trine Zeeberg Iversen
    • 1
    • 2
  • Thomas Moerch Froesig
    • 1
    • 3
  • Shamaila Munir
    • 1
  • Sine Reker Hadrup
    • 1
  • Mads Hald Andersen
    • 1
  • Inge Marie Svane
    • 1
    • 2
  1. 1.Department of Haematology, Center for Cancer Immune Therapy (CCIT)Copenhagen University Hospital, HerlevHerlevDenmark
  2. 2.Department of OncologyCopenhagen University Hospital, HerlevHerlevDenmark
  3. 3.Department of Pharmacology and Pharmacotherapy, Pharmaceutical FacultyUniversity of CopenhagenCopenhagenDenmark

Personalised recommendations