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    Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma.

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    Authors
    Thistlethwaite, Fiona C
    Elkord, Eyad
    Griffiths, Richard W
    Burt, Deborah J
    Shablak, Alaaeldin
    Campbell, John D M
    Gilham, David E
    Austin, Eric B
    Stern, Peter L
    Hawkins, Robert E
    Affiliation
    Cancer Research UK Department of Medical Oncology, University of Manchester and Christie Hospital NHS Foundation Trust, Manchester, UK. fthistlethwaite@PICR.man.ac.uk
    Issue Date
    2008-05
    
    Metadata
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    Abstract
    PURPOSE: CD4(+)CD25(+) regulatory T (T(reg)) cells are present in increased numbers in patients with advanced cancer and CD25(+) T cell depletion potentiates tumour immunity in animal models. The aim of this study was to assess the feasibility and safety of adoptive transfer of CD25(+) depleted autologous T cells in patients with advanced renal cell carcinoma and to examine resulting changes in lymphocyte subsets. PATIENTS AND METHODS: Six patients with advanced renal cell carcinoma underwent leukapheresis followed by conditioning chemotherapy with cyclophosphamide and fludarabine. The autologous leukapheresis product was depleted of CD25(+) cells using CliniMACS System then re-infused into the patient. RESULTS: Efficient CD25(+) depletion from all leukapheresis products was achieved and 0.55-5.87 x 10(7)/kg CD3(+) cells were re-infused. Chemotherapy related haematological toxicity was observed, but blood counts recovered in all patients allowing discharge after a mean inpatient stay of 21 days. One patient subsequently developed a rapidly progressive neurological syndrome. A transient reduction in CD25(+) subset was noted in the peripheral blood of 5 out of 6 patients with evidence of increased T cell responses to PHA in 4 out of 6 patients. One patient showed increased specific proliferative responses to the tumour associated antigen h5T4 coinciding with the nadir of T(reg) cells. CONCLUSIONS: Given the transient nature of the reduction in CD25(+) subset and the observed toxicity there is a need to explore further strategies to improve the safety and efficacy of this approach. Nevertheless, the results provide proof of concept in potentiation of tumour antigen T cell responses when T(reg) cell levels are depleted.
    Citation
    Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma. 2008, 57 (5):623-34 Cancer Immunol. Immunother.
    Journal
    Cancer Immunology, Immunotherapy
    URI
    http://hdl.handle.net/10541/55038
    DOI
    10.1007/s00262-007-0400-6
    PubMed ID
    17899077
    Type
    Article
    Language
    en
    ISSN
    0340-7004
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00262-007-0400-6
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    Immunology
    Medical Oncology

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