Linked Life Data

11714771

Source:http://linkedlifedata.com/resource/pubmed/id/11714771

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-11-20
pubmed:abstractText
Recombinant immunoreceptors with specificity for the carcinoembryonic Ag (CEA) can redirect grafted T cells to a MHC/Ag-independent antitumor response. To analyze receptor-mediated cellular activation in the context of CD28 costimulation, we generated: 1) CEA+ colorectal tumor cells that express simultaneously B7-1 and B7-2, and 2) CEA-specific immunoreceptors that harbor intracellularly the signaling moities either of CD28 (BW431/26-scFv-Fc-CD28), CD3zeta (BW431/26-scFv-Fc-CD3zeta), or FcepsilonRIgamma (BW431/26-scFv-Fc-gamma). By retroviral gene transfer, we grafted activated T cells from the peripheral blood with these immunoreceptors. T cells that express the FcepsilonRIgamma or CD3zeta signaling receptor lysed specifically CEA+ tumor cells and secreted high amounts of IFN-gamma upon receptor cross-linking, whereas anti-CEA-CD28 receptor-grafted T cells did not, indicating that CD28 signaling alone is not sufficient for efficient T cell activation. CD28 costimulation did not affect cytolysis by T cells equipped with gamma- or zeta-signaling receptors, but enhanced both IFN-gamma secretion and proliferation. CD28 costimulation, however, was required for efficient IL-2 secretion of anti-CEA-gamma receptor-grafted T cells. Both purified CD4+ and CD8+ T cells grafted with immunoreceptors required CD28 costimulation for complete T cell activation. We integrated both CD28 and CD3zeta signaling domains into one combined immunoreceptor molecule (BW431/26-scFv-Fc-CD28/CD3zeta) with dual signaling properties. T cells grafted with the combined CD28/CD3zeta signaling receptor secreted high amounts of IL-2 upon Ag binding without exogenous B7/CD28 costimulation, demonstrating that both MHC-independent cellular activation and CD28 costimulation for complete T cell activation can be delivered by one recombinant receptor molecule.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6123-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11714771-Antigens, CD28, pubmed-meshheading:11714771-Antigens, CD3, pubmed-meshheading:11714771-Antigens, CD80, pubmed-meshheading:11714771-Antigens, Neoplasm, pubmed-meshheading:11714771-CD4-Positive T-Lymphocytes, pubmed-meshheading:11714771-CD8-Positive T-Lymphocytes, pubmed-meshheading:11714771-Carcinoembryonic Antigen, pubmed-meshheading:11714771-Coculture Techniques, pubmed-meshheading:11714771-Epitopes, T-Lymphocyte, pubmed-meshheading:11714771-Humans, pubmed-meshheading:11714771-Interleukin-2, pubmed-meshheading:11714771-Lymphocyte Activation, pubmed-meshheading:11714771-Receptors, IgG, pubmed-meshheading:11714771-Receptors, Immunologic, pubmed-meshheading:11714771-Recombinant Proteins, pubmed-meshheading:11714771-Signal Transduction, pubmed-meshheading:11714771-T-Lymphocytes, pubmed-meshheading:11714771-Transfection, pubmed-meshheading:11714771-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule.
pubmed:affiliation
Klinik I für Innere Medizin, Labor Tumorgenetik, Universität zu Köln, Köln, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't