title: Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Medical Oncology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium, Sofie.Wilgenhof@vub.ac.be.
authors.forename: Sofie
authors.initials: S
authors.lastname: Wilgenhof
authors.forename: Jurgen
authors.initials: J
authors.lastname: Corthals
authors.forename: An M T
authors.initials: AM
authors.lastname: Van Nuffel
authors.forename: Daphné
authors.initials: D
authors.lastname: Benteyn
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.forename: Aude
authors.initials: A
authors.lastname: Bonehill
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology; D058965:MART-1 Antigen / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D058950:Melanoma-Specific Antigens / Q000235:genetics; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D016896:Treatment Outcome; D000096142:Cutaneous Malignant Melanoma
chemical_list: D019496:Cancer Vaccines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014442:Monophenol Monooxygenase