PMID- 23620105
OWN - NLM
STAT- MEDLINE
DCOM- 20140107
LR  - 20181202
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 43
IP  - 1
DP  - 2013 Jul
TI  - Silencing of indoleamine 2,3-dioxygenase enhances dendritic cell immunogenicity 
      and antitumour immunity in cancer patients.
PG  - 280-8
LID - 10.3892/ijo.2013.1922 [doi]
AB  - Dendritic cells (DCs) are being explored as a therapeutic vaccine for cancers. 
      However, their immunogenic potential is limited by the presence of 
      immunosuppressive factors. Among these factors is the tryptophan-degrading enzyme 
      indoleamine 2,3-dioxygenase (IDO). In this study, we have investigated the 
      safety, immunogenicity and clinical response of IDO-silenced DC vaccine in four 
      patients with gynecological cancers. DCs were transfected with IDO small 
      interfering RNA and mRNA encoding human telomerase reverse transcriptase (hTERT) 
      or survivin, two universal tumour antigens. Silencing of IDO in DCs did not 
      affect the expression of the co-stimulatory molecules CD80 and CD86, but enhanced 
      the expression of the CCR7 and CD40 molecules. IDO-silenced DCs showed superior 
      potency to activate allogeneic T cells compared to their IDO-positive 
      counterparts. The immunisation with this novel DC cancer vaccine was well 
      tolerated and all patients developed delayed-type hypersensitivity skin reaction 
      and specific T-cell response against hTERT and survivin tumour antigens. Perhaps 
      most importantly, the immune response seen in the patients was related to 
      objective clinical response. Thus, IDO silencing can enhance the immunogenic 
      function of DCs in vitro and in vivo. Overall, the data provide 
      proof-of-principle that immunisation with IDO-silenced DC vaccine is safe and 
      effective in inducing antitumour immunity.
FAU - Sioud, Mouldy
AU  - Sioud M
AD  - Department of Immunology, Oslo University Radium Hospital, Montebello, N-0310 
      Oslo, Norway. mosioud@medisin.uio.no
FAU - Saeboe-Larssen, Stein
AU  - Saeboe-Larssen S
FAU - Hetland, Thea Eline
AU  - Hetland TE
FAU - Kaern, Janne
AU  - Kaern J
FAU - Mobergslien, Anne
AU  - Mobergslien A
FAU - Kvalheim, Gunnar
AU  - Kvalheim G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130425
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Survivin)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Cancer Vaccines/administration & dosage
MH  - Dendritic Cells/*metabolism
MH  - Female
MH  - Gene Silencing
MH  - Genital Neoplasms, Female/*genetics/immunology/pathology/*therapy
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*antagonists & 
      inhibitors/genetics/immunology
MH  - Inhibitor of Apoptosis Proteins/genetics/metabolism
MH  - Middle Aged
MH  - RNA, Small Interfering/genetics
MH  - Survivin
MH  - T-Lymphocytes/immunology/metabolism
MH  - Telomerase/genetics/metabolism
EDAT- 2013/04/27 06:00
MHDA- 2014/01/08 06:00
CRDT- 2013/04/27 06:00
PHST- 2013/01/02 00:00 [received]
PHST- 2013/02/20 00:00 [accepted]
PHST- 2013/04/27 06:00 [entrez]
PHST- 2013/04/27 06:00 [pubmed]
PHST- 2014/01/08 06:00 [medline]
AID - 10.3892/ijo.2013.1922 [doi]
PST - ppublish
SO  - Int J Oncol. 2013 Jul;43(1):280-8. doi: 10.3892/ijo.2013.1922. Epub 2013 Apr 25.