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

Thistlethwaite, FC, Elkord, E, Griffiths, RW, Burt, DJ, Shablak, AM, Campbell, JDM, Gilham, DE, Austin, EB, Stern, PL and Hawkins, RE 2008, 'Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma' , Cancer Immunology, Immunotherapy, 57 (5) , pp. 623-634.

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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.

    Item Type: Article
    Themes: Health and Wellbeing
    Schools: Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Biomedical Research Centre
    Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences
    Journal or Publication Title: Cancer Immunology, Immunotherapy
    Publisher: Springer Verlag
    Refereed: Yes
    ISSN: 0340-7004
    Depositing User: E Elkord
    Date Deposited: 13 Oct 2011 10:36
    Last Modified: 20 Aug 2013 18:13
    URI: http://usir.salford.ac.uk/id/eprint/18282

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