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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-6
pubmed:abstractText
Dendritic cells (DC) transfected with messenger RNA (mRNA) encoding tumor-associated antigens (TAA) are able to induce potent tumor-specific T-cell responses directed to a broad spectrum of tumor-associated epitopes. The in vitro generation of DC possessing all the features crucial for the induction of type 1 immune responses, such as mature state, migratory potential and interleukin-12 (IL-12p70) production is complicated. Particularly migratory potential is inversely correlated with IL-12p70 production after maturation with prostaglandin E2 (PGE2), which is included in maturation cocktails currently used in most vaccination trials. Here, we show that transfection of PGE2 matured DC with a single mRNA strain encoding for ubiquitin followed by a TAA which was linked to IL-12 by a self-cleaving 2A sequence, produced biological active IL-12p70 and were able to present the transfected TAA up to 72 h after transfection. Furthermore, use of the anti-reverse cap analog for in vitro transcription of the IL-12 mRNA enabled constitutive IL-12p70 production for up to 5 days. These transfected mature DC migrated efficiently towards lymph node derived chemokines. DCs constitutively expressing IL-12p70, generate TAA-specific cytotoxic T cells with an high functional avidity, independent of CD4+ T-cell help.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
366-75
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17036057-Antigens, Neoplasm, pubmed-meshheading:17036057-Cancer Vaccines, pubmed-meshheading:17036057-Cells, Cultured, pubmed-meshheading:17036057-Cytotoxicity, Immunologic, pubmed-meshheading:17036057-Cytotoxicity Tests, Immunologic, pubmed-meshheading:17036057-Dendritic Cells, pubmed-meshheading:17036057-Epitopes, pubmed-meshheading:17036057-Gene Therapy, pubmed-meshheading:17036057-Humans, pubmed-meshheading:17036057-Immunophenotyping, pubmed-meshheading:17036057-Immunotherapy, Adoptive, pubmed-meshheading:17036057-Interleukin-12, pubmed-meshheading:17036057-Lymphocyte Activation, pubmed-meshheading:17036057-MART-1 Antigen, pubmed-meshheading:17036057-Neoplasm Proteins, pubmed-meshheading:17036057-RNA, Messenger, pubmed-meshheading:17036057-T-Lymphocytes, Cytotoxic, pubmed-meshheading:17036057-Transfection
pubmed:year
2007
pubmed:articleTitle
Dendritic cells transfected with interleukin-12 and tumor-associated antigen messenger RNA induce high avidity cytotoxic T cells.
pubmed:affiliation
Department of Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. hj.bontkes@vumc.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't