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

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

Thistlethwaite, F., Elkord, E., Griffiths, R., Burt, D., Shablak, A., Campbell, J., …Hawkins, R. (2008). Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma. Cancer Immunology, Immunotherapy, 57(5), 623-634. https://doi.org/10.1007/s00262-007-0400-6

• Journal Article Type: Article
• Publication Date: Jan 1, 2008
• Deposit Date: Oct 13, 2011
• Journal: Cancer Immunology, Immunotherapy
• Print ISSN: 0340-7004
• 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