Show simple item record

dc.contributor.authorGilham, David E
dc.contributor.authorO'Neill, Alison C
dc.contributor.authorHughes, Chris
dc.contributor.authorGuest, Ryan D
dc.contributor.authorKirillova, Natalia
dc.contributor.authorLehane, Margaret
dc.contributor.authorHawkins, Robert E
dc.date.accessioned2009-10-05T15:36:14Z
dc.date.available2009-10-05T15:36:14Z
dc.date.issued2002
dc.identifier.citationPrimary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and neural cell adhesion molecule tumor antigens by CD3zeta-based chimeric immune receptors., 25 (2):139-51 J. Immunother.en
dc.identifier.issn1524-9557
dc.identifier.pmid12074044
dc.identifier.urihttp://hdl.handle.net/10541/83577
dc.description.abstractAntigen-specific T lymphocytes are attractive as potential anticancer agents. The generation of large numbers of antigen-specific T cells is possible through the use of gene therapy to express targeting receptors on the T lymphocyte. Activated T lymphocytes were transduced to express carcino-embryonic antigen or neural cell adhesion molecule targeted CD3zeta chimeric immune receptors. The chimeric receptors were expressed as homodimers and also as heterodimers with the native CD3zeta. T lymphocyte populations were expanded in the absence of selection for the modified cells and were shown to produce cytokines when cultured in the presence of immobilized purified protein antigen. These lymphocytes also responded by cytokine production and cytolytic activity when challenged with tumor-cell lines expressing the antigen recognized by the chimeric immune receptor. The cytolytic activity appears to be largely perforin mediated. Furthermore, soluble carcino-embryonic antigen did not interfere with the functional activity of the carcino-embryonic antigen-targeted lymphocytes. Long-term (5-day) stimulation of the modified lymphocytes by protein antigen resulted in reduced viability similar to that induced by anti-CD3 antibodies alone. Viability was improved by a costimulatory signal indicating that such signals may be vital in the maintenance of long-term functional activity of receptor modified T lymphocytes.
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAntigens, CD3
dc.subject.meshAntigens, CD30
dc.subject.meshAntigens, Neoplasm
dc.subject.meshCarcinoembryonic Antigen
dc.subject.meshCell Death
dc.subject.meshCell Line
dc.subject.meshCytotoxicity, Immunologic
dc.subject.meshHumans
dc.subject.meshImmunotherapy
dc.subject.meshInterferon-gamma
dc.subject.meshLymphocyte Activation
dc.subject.meshNeoplasms
dc.subject.meshNeural Cell Adhesion Molecules
dc.subject.meshRecombinant Fusion Proteins
dc.subject.meshRetroviridae
dc.subject.meshSignal Transduction
dc.subject.meshT-Lymphocytes
dc.subject.meshTransduction, Genetic
dc.titlePrimary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and neural cell adhesion molecule tumor antigens by CD3zeta-based chimeric immune receptors.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Paterson Institute for Cancer Research, University of Manchester, UK.en
dc.identifier.journalJournal of Immunotherapyen
html.description.abstractAntigen-specific T lymphocytes are attractive as potential anticancer agents. The generation of large numbers of antigen-specific T cells is possible through the use of gene therapy to express targeting receptors on the T lymphocyte. Activated T lymphocytes were transduced to express carcino-embryonic antigen or neural cell adhesion molecule targeted CD3zeta chimeric immune receptors. The chimeric receptors were expressed as homodimers and also as heterodimers with the native CD3zeta. T lymphocyte populations were expanded in the absence of selection for the modified cells and were shown to produce cytokines when cultured in the presence of immobilized purified protein antigen. These lymphocytes also responded by cytokine production and cytolytic activity when challenged with tumor-cell lines expressing the antigen recognized by the chimeric immune receptor. The cytolytic activity appears to be largely perforin mediated. Furthermore, soluble carcino-embryonic antigen did not interfere with the functional activity of the carcino-embryonic antigen-targeted lymphocytes. Long-term (5-day) stimulation of the modified lymphocytes by protein antigen resulted in reduced viability similar to that induced by anti-CD3 antibodies alone. Viability was improved by a costimulatory signal indicating that such signals may be vital in the maintenance of long-term functional activity of receptor modified T lymphocytes.


This item appears in the following Collection(s)

Show simple item record