Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma.
AuthorsThistlethwaite, Fiona C
Griffiths, Richard W
Burt, Deborah J
Campbell, John D M
Gilham, David E
Austin, Eric B
Stern, Peter L
Hawkins, Robert E
AffiliationCancer Research UK Department of Medical Oncology, University of Manchester and Christie Hospital NHS Foundation Trust, Manchester, UK. fthistlethwaite@PICR.man.ac.uk
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AbstractPURPOSE: 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.
CitationAdoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma. 2008, 57 (5):623-34 Cancer Immunol. Immunother.
JournalCancer Immunology, Immunotherapy