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Clinical Trial
. 2015 Mar;64(3):381-8.
doi: 10.1007/s00262-014-1642-8. Epub 2014 Dec 30.

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

Sofie Wilgenhof  1 , Jurgen Corthals, An M T Van Nuffel, Daphné Benteyn, Carlo Heirman, Aude Bonehill, Kris Thielemans, Bart Neyns
Affiliations
Clinical Trial

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

Sofie Wilgenhof et al. Cancer Immunol Immunother. 2015 Mar.

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.

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Conflict of interest statement

The use of dendritic cells electroporated with tumor antigen mRNA and TriMix is the topic of a patent (W2009/034172) on which Dr. A. Bonehill and Prof. Dr. K. Thielemans are filed as inventors. None of the authors receive any support or remuneration related to this platform. No potential conflicts of interest were disclosed.

Figures

Fig. 1
Fig. 1
Kaplan–Meier probability curves for relapse-free survival (a) and overall survival (b) in melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases
See this image and copyright information in PMC

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