Killing of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76858
Title:
Killing of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells.
Authors:
Cheadle, Eleanor J; Gilham, David E; Thistlethwaite, Fiona C ( 0000-0002-4832-7008 ) ; Radford, John A ( 0000-0001-7898-2786 ) ; Hawkins, Robert E
Abstract:
Adoptive immunotherapy with tumour-specific T cells is an emerging technology that may be applicable to a broad range of cancers. However, tumours can avoid T cell-mediated attack through multiple mechanisms including downregulation of major histocompatability complex (MHC). Consequently, engineering T cells to target intact protein antigen directly, thus bypassing the need for MHC presentation, can facilitate T cell targeting of tumour cells. Peripheral blood lymphocytes from nine of nine patients with non-Hodgkin lymphoma (NHL) were successfully gene-modified to express a receptor consisting of a CD19 single chain variable fragment (scFv) fused to the T cell CD3zeta signalling molecule. These T cells were functionally active against the CD19(+) Raji Burkitt's lymphoma cell line. Importantly, engineered T cells from seven of nine NHL patients efficiently lysed autologous lymph node tumour biopsy cells. There was a clear correlation between levels of CD19 expression on the tumour and effective killing by the engineered T cells. For two patients with a low or absent CD19(+) cells within the biopsy, no significant killing was observed. These results demonstrate that patients with CD19(+) NHL would be suitable candidates for this form of therapy in the setting of a phase I clinical trial.
Affiliation:
Cancer Research UK Department of Medical Oncology, University of Manchester and Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK.
Citation:
Killing of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells. 2005, 129 (3):322-32 Br. J. Haematol.
Journal:
British Journal of Haematology
Issue Date:
May-2005
URI:
http://hdl.handle.net/10541/76858
DOI:
10.1111/j.1365-2141.2005.05456.x
PubMed ID:
15842655
Type:
Article
Language:
en
ISSN:
0007-1048
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorCheadle, Eleanor J-
dc.contributor.authorGilham, David E-
dc.contributor.authorThistlethwaite, Fiona C-
dc.contributor.authorRadford, John A-
dc.contributor.authorHawkins, Robert E-
dc.date.accessioned2009-08-10T17:31:34Z-
dc.date.available2009-08-10T17:31:34Z-
dc.date.issued2005-05-
dc.identifier.citationKilling of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells. 2005, 129 (3):322-32 Br. J. Haematol.en
dc.identifier.issn0007-1048-
dc.identifier.pmid15842655-
dc.identifier.doi10.1111/j.1365-2141.2005.05456.x-
dc.identifier.urihttp://hdl.handle.net/10541/76858-
dc.description.abstractAdoptive immunotherapy with tumour-specific T cells is an emerging technology that may be applicable to a broad range of cancers. However, tumours can avoid T cell-mediated attack through multiple mechanisms including downregulation of major histocompatability complex (MHC). Consequently, engineering T cells to target intact protein antigen directly, thus bypassing the need for MHC presentation, can facilitate T cell targeting of tumour cells. Peripheral blood lymphocytes from nine of nine patients with non-Hodgkin lymphoma (NHL) were successfully gene-modified to express a receptor consisting of a CD19 single chain variable fragment (scFv) fused to the T cell CD3zeta signalling molecule. These T cells were functionally active against the CD19(+) Raji Burkitt's lymphoma cell line. Importantly, engineered T cells from seven of nine NHL patients efficiently lysed autologous lymph node tumour biopsy cells. There was a clear correlation between levels of CD19 expression on the tumour and effective killing by the engineered T cells. For two patients with a low or absent CD19(+) cells within the biopsy, no significant killing was observed. These results demonstrate that patients with CD19(+) NHL would be suitable candidates for this form of therapy in the setting of a phase I clinical trial.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntigens, CD19-
dc.subject.meshAntigens, CD3-
dc.subject.meshBiopsy-
dc.subject.meshCytotoxicity, Immunologic-
dc.subject.meshFemale-
dc.subject.meshGenetic Vectors-
dc.subject.meshHumans-
dc.subject.meshImmunotherapy, Adoptive-
dc.subject.meshInterferon-gamma-
dc.subject.meshLymphocyte Activation-
dc.subject.meshLymphocyte Transfusion-
dc.subject.meshLymphoma, Non-Hodgkin-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshRetroviridae-
dc.subject.meshT-Lymphocyte Subsets-
dc.subject.meshTransduction, Genetic-
dc.subject.meshTumor Cells, Cultured-
dc.titleKilling of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Department of Medical Oncology, University of Manchester and Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK.en
dc.identifier.journalBritish Journal of Haematologyen

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