Cancer Immunology, Immunotherapy

, Volume 64, Issue 3, pp 381–388 | Cite as

Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases

  • Sofie Wilgenhof
  • Jurgen Corthals
  • An M. T. Van Nuffel
  • Daphné Benteyn
  • Carlo Heirman
  • Aude Bonehill
  • Kris Thielemans
  • Bart Neyns
Original Article

Abstract

Purpose

Melanoma patients with a high risk of recurrence may benefit from immunotherapy with mRNA-electroporated autologous monocyte-derived dendritic cells (DCs). Further benefit may be found in combining DC-therapy with interferon alfa-2b.

Patients and methods

The long-term clinical outcome of AJCC stage III/IV melanoma patients who had no evidence of disease at the time of treatment with autologous mRNA-electroporated DCs in a single-center pilot clinical trial was analyzed. Antigen loading was accomplished by co-electroporation of mRNA encoding a fusion protein between MAGE-A1, -A3, -C2, Tyrosinase, MelanA/MART-1, or gp100, and an HLA class II-targeting sequence. DCs were administered by 4–6 bi-weekly intradermal injections. IFN-α-2b (5 MIU TIW) was initiated either at recurrence (cohort 1), concomitant with DCs (cohorts 2 and 3), or following the fourth DC administration (cohort 4).

Results

Thirty melanoma patients were recruited between April 2006 and June 2009. DC-related adverse events included grade 2 local injection site reactions in all patients, grade 2 fever and flu-like symptoms in one patient, and skin depigmentation in seven patients. After a median follow-up of over 6 years, the median relapse-free survival is 22 months (95 % CI 12–32 months). Twelve patients have died. The median overall survival has not been reached; the 2-year and 4-year survival rates are 93 and 70 %, respectively.

Conclusions

Adjuvant therapy following the resection of melanoma metastases with autologous mRNA-electroporated DCs, combined with interferon alfa-2b, is tolerable and results in encouraging long-term overall survival rates justifying further evaluation in a randomized clinical trial.

Keywords

Dendritic cell Interferon alpha-2b mRNA Immunotherapy Melanoma 

Abbreviations

18F-FDG

18F-fluorodeoxyglucose

AEs

Adverse events

AJCC

American Joint Committee on Cancer

caTLR4

Constitutively active Toll-like receptor 4

CD40L

CD40 ligand

CI

Confidence interval

CTLA-4

Cytotoxic T-lymphocyte-associated antigen 4

CT

Computed tomography

DC

Dendritic cell

DTH

Delayed-type hypersensitivity

GM-CSF

Granulocyte/macrophage colony-stimulating factor

HLA

Human leucocyte antigen

IL-2

Interleukin-2

IL-4

Interleukin-4

IFN-α-2b

Interferon alfa-2b

LDH

Lactate dehydrogenase

MAAs

Melanoma-associated antigens

MAPK

Mitogen-activated protein kinase

MIU

Million international units

MRI

Magnetic resonance imaging

mRNA

Messenger ribonucleic acid

OS

Overall survival

PET–CT

Positron emission tomography–computed tomography

RFS

Relapse-free survival

SKILs

Skin infiltrating lymphocytes

Th1

T helper type 1

TIW

Three times in a week

WHO-PS

World Health Organization Performance Status

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sofie Wilgenhof
    • 1
    • 2
  • Jurgen Corthals
    • 2
  • An M. T. Van Nuffel
    • 2
  • Daphné Benteyn
    • 2
  • Carlo Heirman
    • 2
  • Aude Bonehill
    • 2
  • Kris Thielemans
    • 2
  • Bart Neyns
    • 1
  1. 1.Medical OncologyUniversitair Ziekenhuis BrusselBrusselsBelgium
  2. 2.Laboratory of Molecular and Cellular Therapy and Dendritic Cell-BankVrije Universiteit BrusselBrusselsBelgium

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