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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-11-30
pubmed:abstractText
Exosomes (EXO) derived from tumour cells have been used to stimulate antitumour immune responses, but only resulting in prophylatic immunity. Tumour-derived heat shock protein 70 (HSP70) molecules are molecular chaperones with a broad repertoire of tumour antigen peptides capable of stimulating dendritic cell (DC) maturation and T-cell immune responses. To enhance EXO-based antitumour immunity, we generated an engineered myeloma cell line J558(HSP) expressing endogenous P1A tumour antigen and transgenic form of membrane-bound HSP70 and heat-shocked J558(HS) expressing cytoplasmic HSP70, and purified EXO(HSP) and EXO(HS) from J558(HSP) and J558(HS) tumour cell culture supernatants by ultracentrifugation. We found that EXO(HSP) were able to more efficiently stimulate maturation of DCs with up-regulation of Ia(b) , CD40, CD80 and inflammatory cytokines than EXO(HS) after overnight incubation of immature bone-marrow-derived DCs (5 × 10? cells) with EXO (100 ?g), respectively. We also i.v. immunized BALB/c mice with EXO (30 ?g/mouse) and assessed P1A-specific T-cell responses after immunization. We demonstrate that EXO(HSP) are able to stimulate type 1 CD4(+) helper T (Th1) cell responses, and more efficient P1A-specific CD8(+) cytotoxic T lymphocyte (CTL) responses and antitumour immunity than EXO(HS) . In addition, we further elucidate that EXO(HSP) -stimulated antitumour immunity is mediated by both P1A-specific CD8(+) CTL and non-P1A-specific natural killer (NK) responses. Therefore, membrane-bound HSP70-expressing tumour cell-released EXO may represent a more effective EXO-based vaccine in induction of antitumour immunity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1582-4934
pubmed:author
pubmed:copyrightInfo
© 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2655-66
pubmed:meshHeading
pubmed-meshheading:19627400-Animals, pubmed-meshheading:19627400-Antigens, Neoplasm, pubmed-meshheading:19627400-Blotting, Western, pubmed-meshheading:19627400-CD8-Positive T-Lymphocytes, pubmed-meshheading:19627400-Cell Membrane, pubmed-meshheading:19627400-Cell Proliferation, pubmed-meshheading:19627400-Cytoplasm, pubmed-meshheading:19627400-Exosomes, pubmed-meshheading:19627400-Female, pubmed-meshheading:19627400-Flow Cytometry, pubmed-meshheading:19627400-HSP70 Heat-Shock Proteins, pubmed-meshheading:19627400-Immunization, pubmed-meshheading:19627400-Killer Cells, Natural, pubmed-meshheading:19627400-Mice, pubmed-meshheading:19627400-Mice, Inbred BALB C, pubmed-meshheading:19627400-Multiple Myeloma, pubmed-meshheading:19627400-Protein Engineering, pubmed-meshheading:19627400-T-Lymphocytes, Cytotoxic, pubmed-meshheading:19627400-Tumor Cells, Cultured
pubmed:year
2010
pubmed:articleTitle
Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8(+) CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70.
pubmed:affiliation
Research Unit, Division of Health Research, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't