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

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• 作者：An M. T. Van Nuffel (12)
  Daphné Benteyn (12)
  Sofie Wilgenhof (123)
  Jurgen Corthals (12)
  Carlo Heirman (12)
  Bart Neyns (123)
  Kris Thielemans (123)
  Aude Bonehill (12) Aude.Bonehill@vub.ac.be
• 关键词：Dendritic cell – TriMix – Immunotherapy – Melanoma – Administration route
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2012
• 出版时间：July 2012
• 年：2012
• 卷：61
• 期：7
• 页码：1033-1043
• 全文大小：970.6 KB
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• 作者单位：1. Laboratory of Molecular and Cellular Therapy, Department of Immunology-Physiology, Vrije Universiteit Brussel, Laarbeeklaan 103/E235, 1090 Brussels, Belgium2. The Dendritic Cell Bank, Vrije Universiteit Brussel, Brussels, Belgium3. The Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

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.