FC Thistlethwaite
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; Hawkins, RE
Authors
E Elkord
RW Griffiths
DJ Burt
AM Shablak
JDM Campbell
DE Gilham
EB Austin
PL Stern
RE Hawkins
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.
Journal Article Type | Article |
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Publication Date | Jan 1, 2008 |
Deposit Date | Oct 13, 2011 |
Journal | Cancer Immunology, Immunotherapy |
Print ISSN | 0340-7004 |
Electronic ISSN | 1432-0851 |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 57 |
Issue | 5 |
Pages | 623-634 |
DOI | https://doi.org/10.1007/s00262-007-0400-6 |
Publisher URL | http://dx.doi.org/10.1007/s00262-007-0400-6 |