PMID- 22159452
OWN - NLM
STAT- MEDLINE
DCOM- 20130110
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 61
IP  - 7
DP  - 2012 Jul
TI  - 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.
PG  - 1033-43
LID - 10.1007/s00262-011-1176-2 [doi]
AB  - 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.
FAU - Van Nuffel, An M T
AU  - Van Nuffel AM
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Belgium.
FAU - Benteyn, Daphne
AU  - Benteyn D
FAU - Wilgenhof, Sofie
AU  - Wilgenhof S
FAU - Corthals, Jurgen
AU  - Corthals J
FAU - Heirman, Carlo
AU  - Heirman C
FAU - Neyns, Bart
AU  - Neyns B
FAU - Thielemans, Kris
AU  - Thielemans K
FAU - Bonehill, Aude
AU  - Bonehill A
LA  - eng
PT  - Case Reports
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111210
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (CD27 Ligand)
RN  - 0 (CD70 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 206GF3GB41 (Helium)
RN  - 89210-11-7 (trimix)
RN  - N762921K75 (Nitrogen)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Amino Acid Sequence
MH  - CD27 Ligand/biosynthesis/genetics/immunology
MH  - CD40 Ligand/biosynthesis/genetics/immunology
MH  - Dendritic Cells/*immunology/pathology
MH  - Electroporation/methods
MH  - Helium/*administration & dosage
MH  - Humans
MH  - Hypersensitivity, Delayed/immunology
MH  - Immunotherapy, Adoptive/*methods
MH  - Male
MH  - Melanoma/*immunology/pathology/*therapy
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Neoplasm Staging
MH  - Nitrogen/*administration & dosage
MH  - Oxygen/*administration & dosage
MH  - Prospective Studies
MH  - RNA, Messenger/administration & dosage/genetics
MH  - T-Lymphocytes/*immunology
MH  - Toll-Like Receptor 4/biosynthesis/genetics/immunology
PMC - PMC11028719
COIS- TriMix-DCs are the topic of a current patent application (WO2009/034172). AB and 
      KT are mentioned as inventors of this application. None of the authors involved 
      in this study receives any form of support or remuneration related to this 
      platform.
EDAT- 2011/12/14 06:00
MHDA- 2013/01/11 06:00
PMCR- 2011/12/10
CRDT- 2011/12/14 06:00
PHST- 2011/08/05 00:00 [received]
PHST- 2011/11/25 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2013/01/11 06:00 [medline]
PHST- 2011/12/10 00:00 [pmc-release]
AID - 1176 [pii]
AID - 10.1007/s00262-011-1176-2 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2012 Jul;61(7):1033-43. doi: 
      10.1007/s00262-011-1176-2. Epub 2011 Dec 10.