Eradication of established B-cell lymphoma by CD19-specific murine T cells is dependent on host lymphopenic environment and can be mediated by CD4+ and CD8+ T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74020
Title:
Eradication of established B-cell lymphoma by CD19-specific murine T cells is dependent on host lymphopenic environment and can be mediated by CD4+ and CD8+ T cells.
Authors:
Cheadle, Eleanor J; Hawkins, Robert E; Batha, Hayley; Rothwell, Dominic G; Ashton, Garry; Gilham, David E
Abstract:
B-cell malignancies seem to be particularly amenable to immunotherapy and as such make particularly attractive targets for adoptive T-cell therapy. Murine T cells gene-modified to express a chimeric immune receptor specific for CD19+ (aCD19z) efficiently kill CD19 B-cell lymphoma cells in vitro. aCD19z T cells also secrete high levels of interleukin-2 during culture with target cells in a CD86 independent manner. aCD19z T cells proved effective at eradicating established B-cell lymphoma in a syngeneic model system when combined with a lymphodepleting preconditioning regimen. In mice deficient of T, B, and natural killer cells (severe combined immunodeficient/Beige), aCD19z T cells efficiently eradicated long-term (13 d) established tumors with 100% of treated animals remaining tumor free for greater than 77 days. Although gene-modified CD4+ and CD8+ were both active in this setting, poor engraftment by CD8+ T cells coupled with the rigorous expansion of CD4+ cells in the Balb/c background suggests that CD4+ T cells may be playing a predominant role in lymphoma rejection in this model. Taken together, the therapeutic effectiveness of aCD19z T cells in this model supports a recently opened phase 1 trial of this receptor in non-Hodgkin lymphoma.
Affiliation:
Department of Medical Oncology, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK. echeadle@picr.man.ac.uk
Citation:
Eradication of established B-cell lymphoma by CD19-specific murine T cells is dependent on host lymphopenic environment and can be mediated by CD4+ and CD8+ T cells. 2009, 32 (3):207-18 J. Immunother.
Journal:
Journal of Immunotherapy
Issue Date:
Apr-2009
URI:
http://hdl.handle.net/10541/74020
DOI:
10.1097/CJI.0b013e318194a921
PubMed ID:
19242379
Type:
Article
Language:
en
ISSN:
1537-4513
Appears in Collections:
All Paterson Institute for Cancer Research; Medical Oncology; Histology

Full metadata record

DC FieldValue Language
dc.contributor.authorCheadle, Eleanor J-
dc.contributor.authorHawkins, Robert E-
dc.contributor.authorBatha, Hayley-
dc.contributor.authorRothwell, Dominic G-
dc.contributor.authorAshton, Garry-
dc.contributor.authorGilham, David E-
dc.date.accessioned2009-07-15T16:19:19Z-
dc.date.available2009-07-15T16:19:19Z-
dc.date.issued2009-04-
dc.identifier.citationEradication of established B-cell lymphoma by CD19-specific murine T cells is dependent on host lymphopenic environment and can be mediated by CD4+ and CD8+ T cells. 2009, 32 (3):207-18 J. Immunother.en
dc.identifier.issn1537-4513-
dc.identifier.pmid19242379-
dc.identifier.doi10.1097/CJI.0b013e318194a921-
dc.identifier.urihttp://hdl.handle.net/10541/74020-
dc.description.abstractB-cell malignancies seem to be particularly amenable to immunotherapy and as such make particularly attractive targets for adoptive T-cell therapy. Murine T cells gene-modified to express a chimeric immune receptor specific for CD19+ (aCD19z) efficiently kill CD19 B-cell lymphoma cells in vitro. aCD19z T cells also secrete high levels of interleukin-2 during culture with target cells in a CD86 independent manner. aCD19z T cells proved effective at eradicating established B-cell lymphoma in a syngeneic model system when combined with a lymphodepleting preconditioning regimen. In mice deficient of T, B, and natural killer cells (severe combined immunodeficient/Beige), aCD19z T cells efficiently eradicated long-term (13 d) established tumors with 100% of treated animals remaining tumor free for greater than 77 days. Although gene-modified CD4+ and CD8+ were both active in this setting, poor engraftment by CD8+ T cells coupled with the rigorous expansion of CD4+ cells in the Balb/c background suggests that CD4+ T cells may be playing a predominant role in lymphoma rejection in this model. Taken together, the therapeutic effectiveness of aCD19z T cells in this model supports a recently opened phase 1 trial of this receptor in non-Hodgkin lymphoma.en
dc.language.isoenen
dc.subjectHaematologic Canceren
dc.subject.meshAnimals-
dc.subject.meshAntigens, CD19-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshCD4-Positive T-Lymphocytes-
dc.subject.meshCD8-Positive T-Lymphocytes-
dc.subject.meshCyclophosphamide-
dc.subject.meshHematologic Neoplasms-
dc.subject.meshHumans-
dc.subject.meshImmunotherapy, Adoptive-
dc.subject.meshLymphoma, B-Cell-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshProtein Engineering-
dc.subject.meshTransduction, Genetic-
dc.titleEradication of established B-cell lymphoma by CD19-specific murine T cells is dependent on host lymphopenic environment and can be mediated by CD4+ and CD8+ T cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK. echeadle@picr.man.ac.uken
dc.identifier.journalJournal of Immunotherapyen
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