Linked Life Data

11986228

Source:http://linkedlifedata.com/resource/pubmed/id/11986228

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-5-2
pubmed:abstractText
Recognition of the essential role of dendritic cells (DCs) as professional antigen-presenting cells has prompted investigators to search for methods to use DCs as natural adjuvants in immunotherapy. A number of antigenic oligopeptides, recognized by CD8(+) cytotoxic T lymphocytes (CTLs) specific for cancer cells, have been applied in clinical trials using DCs. Such a monovalent vaccine with a single epitope for a particular type of HLA class 1 molecule would be effective. However, a polyvalent vaccine might be more potent. We designed a novel protein delivery system consisting of hydrophobized polysaccharides complexed with target proteins. The truncated HER2 protein encompassing 147 N-terminal amino acids, including the 9-mer HER2p63-71 peptide (HER2p63), TYLPTNASL, the human homologue of an antigenic murine tumor rejection peptide, was prepared. We report here that HLA-A2402(+) DCs could incorporate hydrophobized polysaccharide-truncated HER2 protein complexes and process the protein to present major histocompatibility complex class 1-binding HER2p63 peptide. The complexes enter DCs by phagocytosis, and then the truncated protein is processed through a pathway similar to that for endogenous proteins. DCs sensitized by these complexes primed and boosted HER2p63-specific CD8(+) T cells in the context of HLA-A2402. Vaccination with DCs incorporating these complexes completely suppressed lung metastases in a HER2-expressing murine tumor model. We also generated 3 CD4(+) clones reactive with different HER2- derived 25-mer peptides from lymph node cells in mice treated with CHP/HER2-147. Thus, hydrophobized polysaccharide-protein complexes are promising candidates for the construction of polyvalent vaccines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3717-24
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11986228-Amino Acid Sequence, pubmed-meshheading:11986228-Animals, pubmed-meshheading:11986228-Antigen Presentation, pubmed-meshheading:11986228-Antigens, Neoplasm, pubmed-meshheading:11986228-CD4-Positive T-Lymphocytes, pubmed-meshheading:11986228-Cancer Vaccines, pubmed-meshheading:11986228-Cells, Cultured, pubmed-meshheading:11986228-Clone Cells, pubmed-meshheading:11986228-Dendritic Cells, pubmed-meshheading:11986228-Female, pubmed-meshheading:11986228-Glucans, pubmed-meshheading:11986228-HLA-A Antigens, pubmed-meshheading:11986228-HLA-A24 Antigen, pubmed-meshheading:11986228-Humans, pubmed-meshheading:11986228-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:11986228-Macromolecular Substances, pubmed-meshheading:11986228-Mice, pubmed-meshheading:11986228-Mice, Inbred BALB C, pubmed-meshheading:11986228-Monocytes, pubmed-meshheading:11986228-Neoplasms, pubmed-meshheading:11986228-Peptide Fragments, pubmed-meshheading:11986228-Polysaccharides, pubmed-meshheading:11986228-Receptor, erbB-2, pubmed-meshheading:11986228-T-Lymphocytes, Cytotoxic
pubmed:year
2002
pubmed:articleTitle
Presentation of a major histocompatibility complex class 1-binding peptide by monocyte-derived dendritic cells incorporating hydrophobized polysaccharide-truncated HER2 protein complex: implications for a polyvalent immuno-cell therapy.
pubmed:affiliation
Second Department of Internal Medicine, the Department of Obstetrics and Gynecology, Mie University School of Medicine, Tsu, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't