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.

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 (18)F-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.

• Authors: An M T Van Nuffel, Daphné Benteyn, Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Bart Neyns, Kris Thielemans, Aude Bonehill
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 61 Issue 7 Pg. 1033-43 (Jul 2012) ISSN: 1432-0851 [Electronic] Germany
• PMID: 22159452 (Publication Type: Case Reports, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD27 Ligand
• CD70 protein, human
• RNA, Messenger
• TLR4 protein, human
• Toll-Like Receptor 4
• CD40 Ligand
• Helium
• trimix
• Nitrogen
• Oxygen

Topics

• Amino Acid Sequence
• CD27 Ligand (biosynthesis, genetics, immunology)
• CD40 Ligand (biosynthesis, genetics, immunology)
• Dendritic Cells (immunology, pathology)
• Electroporation (methods)
• Helium (administration & dosage)
• Humans
• Hypersensitivity, Delayed (immunology)
• Immunotherapy, Adoptive (methods)
• Male
• Melanoma (immunology, pathology, therapy)
• Middle Aged
• Molecular Sequence Data
• Neoplasm Staging
• Nitrogen (administration & dosage)
• Oxygen (administration & dosage)
• Prospective Studies
• RNA, Messenger (administration & dosage, genetics)
• T-Lymphocytes (immunology)
• Toll-Like Receptor 4 (biosynthesis, genetics, immunology)