Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72736
Title:
Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo.
Authors:
Biglari, Alireza; Southgate, Thomas D; Fairbairn, Leslie J; Gilham, David E
Abstract:
Antibody-dependent cellular cytotoxicity (ADCC) is one means by which macrophages (as well as natural killer cells and granulocytes) elicit a cytotoxic response. This is achieved via interaction of the Fc-gamma-receptor (CD64) with the Fc portion of antibody bound to target cells. We have created a chimeric CD64 molecule that incorporates a single chain Fv molecule, targeted against human carcinoembryonic antigen (CEA), fused to the membrane spanning and cytosolic domains of human CD64. Following adenoviral transfer to primary human monocytes, this chimeric CD64 receptor induced antigen-specific cytokine secretion during culture on immobilised CEA protein or on CEA-expressing tumour cells. Moreover, CEA targeted, but not control, monocytes effectively retarded CEA-positive tumour cell growth in vitro. Importantly, targeted monocyte cultures significantly reduced in vivo tumour growth rates in xenograft studies resulting in improved survival rates over that of control monocyte cultures. These data suggest that genetically directing monocytes against tumour antigens may be a useful means of achieving an immunotherapeutic response.
Affiliation:
Cancer Research UK Gene Therapy Group and Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo. 2006, 13 (7):602-10 Gene Ther.
Journal:
Gene Therapy
Issue Date:
Apr-2006
URI:
http://hdl.handle.net/10541/72736
DOI:
10.1038/sj.gt.3302706
PubMed ID:
16397508
Type:
Article
Language:
en
ISSN:
0969-7128
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBiglari, Alireza-
dc.contributor.authorSouthgate, Thomas D-
dc.contributor.authorFairbairn, Leslie J-
dc.contributor.authorGilham, David E-
dc.date.accessioned2009-07-07T11:13:33Z-
dc.date.available2009-07-07T11:13:33Z-
dc.date.issued2006-04-
dc.identifier.citationHuman monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo. 2006, 13 (7):602-10 Gene Ther.en
dc.identifier.issn0969-7128-
dc.identifier.pmid16397508-
dc.identifier.doi10.1038/sj.gt.3302706-
dc.identifier.urihttp://hdl.handle.net/10541/72736-
dc.description.abstractAntibody-dependent cellular cytotoxicity (ADCC) is one means by which macrophages (as well as natural killer cells and granulocytes) elicit a cytotoxic response. This is achieved via interaction of the Fc-gamma-receptor (CD64) with the Fc portion of antibody bound to target cells. We have created a chimeric CD64 molecule that incorporates a single chain Fv molecule, targeted against human carcinoembryonic antigen (CEA), fused to the membrane spanning and cytosolic domains of human CD64. Following adenoviral transfer to primary human monocytes, this chimeric CD64 receptor induced antigen-specific cytokine secretion during culture on immobilised CEA protein or on CEA-expressing tumour cells. Moreover, CEA targeted, but not control, monocytes effectively retarded CEA-positive tumour cell growth in vitro. Importantly, targeted monocyte cultures significantly reduced in vivo tumour growth rates in xenograft studies resulting in improved survival rates over that of control monocyte cultures. These data suggest that genetically directing monocytes against tumour antigens may be a useful means of achieving an immunotherapeutic response.en
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectCancer Transplantationen
dc.subjectCanceren
dc.subject.meshAnimals-
dc.subject.meshCarcinoembryonic Antigen-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCells, Cultured-
dc.subject.meshCytokines-
dc.subject.meshGene Therapy-
dc.subject.meshGenetic Engineering-
dc.subject.meshGreen Fluorescent Proteins-
dc.subject.meshHumans-
dc.subject.meshImmunotherapy-
dc.subject.meshKiller Cells, Natural-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshMonocytes-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshNeoplasms-
dc.subject.meshReceptors, IgG-
dc.subject.meshRecombinant Proteins-
dc.subject.meshT-Lymphocytes-
dc.subject.meshTransplantation, Heterologous-
dc.titleHuman monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Gene Therapy Group and Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalGene Therapyen

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