Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/55038
Title:
Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma.
Authors:
Thistlethwaite, Fiona C ( 0000-0002-4832-7008 ) ; Elkord, Eyad; Griffiths, Richard W; Burt, Deborah J; Shablak, Alaaeldin; Campbell, John D M; Gilham, David E; Austin, Eric B; Stern, Peter L; Hawkins, Robert E
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.
Affiliation:
Cancer Research UK Department of Medical Oncology, University of Manchester and Christie Hospital NHS Foundation Trust, Manchester, UK. fthistlethwaite@PICR.man.ac.uk
Citation:
Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma. 2008, 57 (5):623-34 Cancer Immunol. Immunother.
Journal:
Cancer Immunology, Immunotherapy
Issue Date:
May-2008
URI:
http://hdl.handle.net/10541/55038
DOI:
10.1007/s00262-007-0400-6
PubMed ID:
17899077
Type:
Article
Language:
en
ISSN:
0340-7004
Appears in Collections:
All Paterson Institute for Cancer Research; Immunology; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorThistlethwaite, Fiona C-
dc.contributor.authorElkord, Eyad-
dc.contributor.authorGriffiths, Richard W-
dc.contributor.authorBurt, Deborah J-
dc.contributor.authorShablak, Alaaeldin-
dc.contributor.authorCampbell, John D M-
dc.contributor.authorGilham, David E-
dc.contributor.authorAustin, Eric B-
dc.contributor.authorStern, Peter L-
dc.contributor.authorHawkins, Robert E-
dc.date.accessioned2009-03-12T17:15:40Z-
dc.date.available2009-03-12T17:15:40Z-
dc.date.issued2008-05-
dc.identifier.citationAdoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma. 2008, 57 (5):623-34 Cancer Immunol. Immunother.en
dc.identifier.issn0340-7004-
dc.identifier.pmid17899077-
dc.identifier.doi10.1007/s00262-007-0400-6-
dc.identifier.urihttp://hdl.handle.net/10541/55038-
dc.description.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.en
dc.language.isoenen
dc.subjectRegulatory T Cellsen
dc.subjectCD25en
dc.subjectFOXP3en
dc.subjectAdoptive Cell Therapyen
dc.subjectConditioning Chemotherapyen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntigens, CD3-
dc.subject.meshCarcinoma, Renal Cell-
dc.subject.meshFemale-
dc.subject.meshFlow Cytometry-
dc.subject.meshHumans-
dc.subject.meshImmunotherapy, Adoptive-
dc.subject.meshKidney Neoplasms-
dc.subject.meshLeukapheresis-
dc.subject.meshLymphocyte Depletion-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshT-Lymphocytes-
dc.subject.meshT-Lymphocytes, Regulatory-
dc.subject.meshTransplantation, Autologous-
dc.titleAdoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Department of Medical Oncology, University of Manchester and Christie Hospital NHS Foundation Trust, Manchester, UK. fthistlethwaite@PICR.man.ac.uken
dc.identifier.journalCancer Immunology, Immunotherapyen

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