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

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

Research output: Contribution to journalArticle

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Abstract

Purpose: CD4+CD25+ regulatory T (Treg) 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 Treg 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 Treg cell levels are depleted.

Original languageEnglish
Pages (from-to)623-634
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume57
Issue number5
DOIs
Publication statusPublished - May 2008
Externally publishedYes

Fingerprint

Adoptive Transfer
Renal Cell Carcinoma
T-Lymphocytes
Regulatory T-Lymphocytes
Leukapheresis
Neoplasm Antigens
Safety
Drug Therapy
Patient Discharge
Lymphocyte Subsets
Cyclophosphamide
Inpatients
Immunity
Neoplasms
Animal Models

Keywords

  • Adoptive cell therapy
  • CD25
  • Conditioning chemotherapy
  • FOXP3
  • Regulatory T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Thistlethwaite, F. C., Elkord, E., Griffiths, R. W., Burt, D. J., Shablak, A. M., Campbell, J. D. M., ... Hawkins, R. E. (2008). Adoptive transfer of Treg 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

Adoptive transfer of Treg depleted autologous T cells in advanced renal cell carcinoma. / Thistlethwaite, Fiona C.; Elkord, Eyad; Griffiths, Richard W.; Burt, Deborah J.; Shablak, Alaaeldin M.; Campbell, John D.M.; Gilham, David E.; Austin, Eric B.; Stern, Peter L.; Hawkins, Robert E.

In: Cancer Immunology, Immunotherapy, Vol. 57, No. 5, 05.2008, p. 623-634.

Research output: Contribution to journalArticle

Thistlethwaite, FC, Elkord, E, Griffiths, RW, Burt, DJ, Shablak, AM, Campbell, JDM, Gilham, DE, Austin, EB, Stern, PL & Hawkins, RE 2008, 'Adoptive transfer of Treg depleted autologous T cells in advanced renal cell carcinoma', Cancer Immunology, Immunotherapy, vol. 57, no. 5, pp. 623-634. https://doi.org/10.1007/s00262-007-0400-6
Thistlethwaite, Fiona C. ; Elkord, Eyad ; Griffiths, Richard W. ; Burt, Deborah J. ; Shablak, Alaaeldin M. ; Campbell, John D.M. ; Gilham, David E. ; Austin, Eric B. ; Stern, Peter L. ; Hawkins, Robert E. / Adoptive transfer of Treg depleted autologous T cells in advanced renal cell carcinoma. In: Cancer Immunology, Immunotherapy. 2008 ; Vol. 57, No. 5. pp. 623-634.
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AU - Elkord, Eyad

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AU - Shablak, Alaaeldin M.

AU - Campbell, John D.M.

AU - Gilham, David E.

AU - Austin, Eric B.

AU - Stern, Peter L.

AU - Hawkins, Robert E.

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