Cancer Immunology, Immunotherapy

, Volume 61, Issue 7, pp 1033–1043

Intravenous and intradermal TriMix-dendritic cell therapy results in a broad T-cell response and durable tumor response in a chemorefractory stage IV-M1c melanoma patient

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

Abstract

Dendritic cells (DCs) electroporated with mRNA encoding CD70, CD40L and a constitutively active toll-like receptor 4 (TriMix-DC) have an increased T-cell stimulatory capacity. In a prospective phase IB clinical trial, we treated melanoma patients with intradermal and intravenous injections of autologous TriMix-DC co-electroporated with mRNA encoding full-length MAGE-A3, MAGE-C2, tyrosinase and gp100. We report here the immunological and clinical results obtained in one patient with a particularly favorable outcome. This patient had stage IV-M1c melanoma with documented progression during dacarbazine chemotherapy and received 5 TriMix-DC injections. Following DC therapy, a broad CD8+ T-cell response against multiple epitopes derived from all four treatment antigens was found in the blood and among T cells derived from DTH biopsy. In addition, CD4+ T cells recognizing different MAGE-A3-derived epitopes were detected in DTH-derived cells. A spontaneous anti-MAGE-C2 CD8+ T-cell response was present prior to TriMix-DC therapy and increased during treatment. The tumor response was assessed with 18-fluorodeoxyglucose-positron emission/computed tomography. We documented a partial tumor response according to RECIST criteria with a marked reduction in 18F-FDG-uptake by lung, lymph node and bone metastases. The patient remains free from progression after 12 months of follow-up. This case report indicates that administration of autologous TriMix-DC by the combined intradermal and intravenous route can mediate a durable objective tumor response accompanied by a broad T-cell response in a chemorefractory stage IV-M1c melanoma patient.

Keywords

Dendritic cell TriMix Immunotherapy Melanoma Administration route 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • An M. T. Van Nuffel
    • 1
    • 2
  • Daphné Benteyn
    • 1
    • 2
  • Sofie Wilgenhof
    • 1
    • 2
    • 3
  • Jurgen Corthals
    • 1
    • 2
  • Carlo Heirman
    • 1
    • 2
  • Bart Neyns
    • 1
    • 2
    • 3
  • Kris Thielemans
    • 1
    • 2
    • 3
  • Aude Bonehill
    • 1
    • 2
  1. 1.Laboratory of Molecular and Cellular Therapy, Department of Immunology-PhysiologyVrije Universiteit BrusselBrusselsBelgium
  2. 2.The Dendritic Cell Bank, Vrije Universiteit BrusselBrusselsBelgium
  3. 3.The Department of Medical OncologyUniversitair Ziekenhuis BrusselBrusselsBelgium

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