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01-05-2008 | Original Article

Adoptive transfer of T_reg depleted autologous T cells in advanced renal cell carcinoma

Authors: Fiona C. Thistlethwaite, Eyad Elkord, Richard W. Griffiths, Deborah J. Burt, Alaaeldin M. Shablak, John D. M. Campbell, David E. Gilham, Eric B. Austin, Peter L. Stern, Robert E. Hawkins

Published in: Cancer Immunology, Immunotherapy | Issue 5/2008

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 × 10⁷/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.

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Title: Adoptive transfer of Treg depleted autologous T cells in advanced renal cell carcinoma
Authors: Fiona C. Thistlethwaite
Eyad Elkord
Richard W. Griffiths
Deborah J. Burt
Alaaeldin M. Shablak
John D. M. Campbell
David E. Gilham
Eric B. Austin
Peter L. Stern
Robert E. Hawkins
Publication date: 01-05-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 5/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0400-6

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