Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86669
Title:
Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.
Authors:
Brown, Michael D; Zhang, Y; Dermime, Said; De Wynter, Erika A; Hart, Claire A; Kitchener, Henry C; Stern, Peter L; Skinner, M A; Stacey, S N
Abstract:
The identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line DC2.4. The infected DC2.4 cells were found to stimulate the T-T cell hybridoma line RF33. 70, which responds specifically to the MHC class I restricted OVA peptide SIINFEKL. The stimulatory ability of the rFWPV-infected DC2.4 cells lasted for at least 72 h after infection and was eventually limited by proliferation of uninfected cells. By comparison, DC2.4 cells pulsed with synthetic SIINFEKL peptide stimulated RF33.70 well initially, but the stimulatory ability had declined to zero by 24 h after pulsing. FWPV infection of DC2.4 up-regulated MHC and costimulatory molecule expression. rFWPV was also found to infect both immature and mature human DC derived from cord blood CD34+ progenitors and express transgenes for up to 20 days after infection. We conclude that rFWPV shows promise as a vector for antigen gene transfer to DC in tumour immunotherapy protocols.
Affiliation:
Cancer Research Campaign Laboratories, Paterson Institute of Cancer Research, Christie Hospital, Manchester, UK.
Citation:
Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity. 2000, 7 (19):1680-9 Gene Ther.
Journal:
Gene Therapy
Issue Date:
Oct-2000
URI:
http://hdl.handle.net/10541/86669
DOI:
10.1038/sj.gt.3301288
PubMed ID:
11083477
Type:
Article
Language:
en
ISSN:
0969-7128
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBrown, Michael Den
dc.contributor.authorZhang, Yen
dc.contributor.authorDermime, Saiden
dc.contributor.authorDe Wynter, Erika Aen
dc.contributor.authorHart, Claire Aen
dc.contributor.authorKitchener, Henry Cen
dc.contributor.authorStern, Peter Len
dc.contributor.authorSkinner, M Aen
dc.contributor.authorStacey, S Nen
dc.date.accessioned2009-11-23T12:02:18Z-
dc.date.available2009-11-23T12:02:18Z-
dc.date.issued2000-10-
dc.identifier.citationDendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity. 2000, 7 (19):1680-9 Gene Ther.en
dc.identifier.issn0969-7128-
dc.identifier.pmid11083477-
dc.identifier.doi10.1038/sj.gt.3301288-
dc.identifier.urihttp://hdl.handle.net/10541/86669-
dc.description.abstractThe identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line DC2.4. The infected DC2.4 cells were found to stimulate the T-T cell hybridoma line RF33. 70, which responds specifically to the MHC class I restricted OVA peptide SIINFEKL. The stimulatory ability of the rFWPV-infected DC2.4 cells lasted for at least 72 h after infection and was eventually limited by proliferation of uninfected cells. By comparison, DC2.4 cells pulsed with synthetic SIINFEKL peptide stimulated RF33.70 well initially, but the stimulatory ability had declined to zero by 24 h after pulsing. FWPV infection of DC2.4 up-regulated MHC and costimulatory molecule expression. rFWPV was also found to infect both immature and mature human DC derived from cord blood CD34+ progenitors and express transgenes for up to 20 days after infection. We conclude that rFWPV shows promise as a vector for antigen gene transfer to DC in tumour immunotherapy protocols.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAnimals-
dc.subject.meshAntigens, CD34-
dc.subject.meshCells, Cultured-
dc.subject.meshChickens-
dc.subject.meshCoturnix-
dc.subject.meshDendritic Cells-
dc.subject.meshFowlpox virus-
dc.subject.meshGene Expression-
dc.subject.meshGene Therapy-
dc.subject.meshHistocompatibility Antigens Class I-
dc.subject.meshHumans-
dc.subject.meshHybridomas-
dc.subject.meshImmunotherapy-
dc.subject.meshLac Operon-
dc.subject.meshMice-
dc.subject.meshOvalbumin-
dc.subject.meshT-Lymphocytes, Cytotoxic-
dc.subject.meshTransgenes-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshVaccinia virus-
dc.titleDendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Laboratories, Paterson Institute of Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalGene Therapyen

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