Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76838
Title:
Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy.
Authors:
Griffiths, Richard W; Gilham, David E; Dangoor, Adam; Ramani, Vijay A C; Clarke, Noel W ( 0000-0001-7776-8059 ) ; Stern, Peter L; Hawkins, Robert E
Abstract:
The 5T4 oncofoetal antigen is a heavily glycosylated cell surface protein found on human placental trophoblast and on diverse types of human cancer but is not expressed at significant levels on adult human tissues in health. It therefore satisfies the criteria for a tumour-associated antigen and is an ideal target for the immunotherapy of cancer. We report here that 5T4 is strongly expressed on the majority of renal cell carcinomas and therefore this population of patients is suitable for trials of 5T4-targeted therapies. In particular, we have shown that T cells from renal cell carcinoma patients can be genetically modified to kill 5T4 expressing renal cancer cell lines by introduction of a chimeric-signalling protein. This protein consists of a single chain antibody fragment capable of binding antigen directly at the cell surface and then activating the T cell by virtue of a CD3zeta-signalling domain. This is a powerful tool that bypasses a number of mechanisms that allow tumours to escape T-cell killing and can be readily scaled up for clinical use.
Affiliation:
Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Research Centre, Manchester M20 4BX, UK.
Citation:
Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy. 2005, 93 (6):670-7 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
19-Sep-2005
URI:
http://hdl.handle.net/10541/76838
DOI:
10.1038/sj.bjc.6602776
PubMed ID:
16222313
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorGriffiths, Richard W-
dc.contributor.authorGilham, David E-
dc.contributor.authorDangoor, Adam-
dc.contributor.authorRamani, Vijay A C-
dc.contributor.authorClarke, Noel W-
dc.contributor.authorStern, Peter L-
dc.contributor.authorHawkins, Robert E-
dc.date.accessioned2009-08-10T17:21:39Z-
dc.date.available2009-08-10T17:21:39Z-
dc.date.issued2005-09-19-
dc.identifier.citationExpression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy. 2005, 93 (6):670-7 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid16222313-
dc.identifier.doi10.1038/sj.bjc.6602776-
dc.identifier.urihttp://hdl.handle.net/10541/76838-
dc.description.abstractThe 5T4 oncofoetal antigen is a heavily glycosylated cell surface protein found on human placental trophoblast and on diverse types of human cancer but is not expressed at significant levels on adult human tissues in health. It therefore satisfies the criteria for a tumour-associated antigen and is an ideal target for the immunotherapy of cancer. We report here that 5T4 is strongly expressed on the majority of renal cell carcinomas and therefore this population of patients is suitable for trials of 5T4-targeted therapies. In particular, we have shown that T cells from renal cell carcinoma patients can be genetically modified to kill 5T4 expressing renal cancer cell lines by introduction of a chimeric-signalling protein. This protein consists of a single chain antibody fragment capable of binding antigen directly at the cell surface and then activating the T cell by virtue of a CD3zeta-signalling domain. This is a powerful tool that bypasses a number of mechanisms that allow tumours to escape T-cell killing and can be readily scaled up for clinical use.en
dc.language.isoenen
dc.subjectRenal Canceren
dc.subjectKidney Canceren
dc.subject.meshAdenocarcinoma, Clear Cell-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntigens, Neoplasm-
dc.subject.meshApoptosis-
dc.subject.meshCarcinoma, Papillary-
dc.subject.meshCarcinoma, Renal Cell-
dc.subject.meshChromium-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshFlow Cytometry-
dc.subject.meshHumans-
dc.subject.meshImmunotherapy-
dc.subject.meshInterferon-gamma-
dc.subject.meshKidney Neoplasms-
dc.subject.meshMale-
dc.subject.meshMembrane Glycoproteins-
dc.subject.meshMiddle Aged-
dc.subject.meshT-Lymphocytes-
dc.titleExpression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Paterson Institute for Cancer Research, Christie Research Centre, Manchester M20 4BX, UK.en
dc.identifier.journalBritish Journal of Canceren

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