OBJECTIVE: Immunotherapy targeting the Wilms' tumour 1 gene product has been proven safe and effective for treating malignant glioma in a phase II clinical study. Currently, radiation/temozolomide therapy is the standard treatment with only modest benefit. Whether combining radiation/temozolomide therapy with WT1 immunotherapy will have a negating effect on immunotherapy is still controversial because of the significant lymphocytopaenia induced by the former therapy. To address this issue, we investigated the changes in frequency and number of WT1-specific T-cells in patients with malignant gliomas. METHODS: Twenty-two patients with newly diagnosed malignant glioma who received standard radiation/temozolomide therapy were recruited for the study. Blood samples were collected before treatment and on the sixth week of therapy. The frequencies and numbers of lymphocytes, CD8(+) T-cells, WT1-specific T-cells, regulatory T-cells, natural killer cells and natural killer T-cells were measured and analysed using T-tests. RESULTS: Analysis of the frequency of T lymphocytes and its subpopulation showed an increase in regulatory T-cells, but no significant change was noted in the populations of T-cells, WT1-specific T-cells, NK cells and NKT cells. Reductions in the total numbers of T-cells, WT1-specific T-cells, NK cells and NKT cells were mainly a consequence of the decrease in the total lymphocyte count. CONCLUSIONS: Radiation/temozolomide therapy did not significantly affect the frequency of WT1-specific T-cells, suggesting that the combination with WT1 immunotherapy may be possible, although further assessment in the clinical setting is warranted.
OBJECTIVE: Immunotherapy targeting the Wilms' tumour 1 gene product has been proven safe and effective for treating malignant glioma in a phase II clinical study. Currently, radiation/temozolomide therapy is the standard treatment with only modest benefit. Whether combining radiation/temozolomide therapy with WT1 immunotherapy will have a negating effect on immunotherapy is still controversial because of the significant lymphocytopaenia induced by the former therapy. To address this issue, we investigated the changes in frequency and number of WT1-specific T-cells in patients with malignant gliomas. METHODS: Twenty-two patients with newly diagnosed malignant glioma who received standard radiation/temozolomide therapy were recruited for the study. Blood samples were collected before treatment and on the sixth week of therapy. The frequencies and numbers of lymphocytes, CD8(+) T-cells, WT1-specific T-cells, regulatory T-cells, natural killer cells and natural killer T-cells were measured and analysed using T-tests. RESULTS: Analysis of the frequency of T lymphocytes and its subpopulation showed an increase in regulatory T-cells, but no significant change was noted in the populations of T-cells, WT1-specific T-cells, NK cells and NKT cells. Reductions in the total numbers of T-cells, WT1-specific T-cells, NK cells and NKT cells were mainly a consequence of the decrease in the total lymphocyte count. CONCLUSIONS: Radiation/temozolomide therapy did not significantly affect the frequency of WT1-specific T-cells, suggesting that the combination with WT1 immunotherapy may be possible, although further assessment in the clinical setting is warranted.
Authors: Camilo E Fadul; Jan L Fisher; Thomas H Hampton; Enrico C Lallana; Zhongze Li; Jiang Gui; Zbigniew M Szczepiorkowski; Tor D Tosteson; C Harker Rhodes; Heather A Wishart; Lionel D Lewis; Marc S Ernstoff Journal: J Immunother Date: 2011-05 Impact factor: 4.456
Authors: Camilo E Fadul; Jan L Fisher; Jiang Gui; Thomas H Hampton; Anik L Côté; Marc S Ernstoff Journal: Neuro Oncol Date: 2011-02-20 Impact factor: 12.300
Authors: Roy Rampling; Sharon Peoples; Paul J Mulholland; Allan James; Omar Al-Salihi; Christopher J Twelves; Catherine McBain; Sarah Jefferies; Alan Jackson; Willie Stewart; Juha Lindner; Sarah Kutscher; Norbert Hilf; Lesley McGuigan; Jane Peters; Karen Hill; Oliver Schoor; Harpreet Singh-Jasuja; Sarah E Halford; James W A Ritchie Journal: Clin Cancer Res Date: 2016-05-25 Impact factor: 12.531