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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.
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
html.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.


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