TY - JOUR
T1 - Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients
AU - Fujita, Tetsuo
AU - Teh, Bin S.
AU - Timme, Terry L.
AU - Mai, Wei Yuan
AU - Satoh, Takefumi
AU - Kusaka, Nobuyuki
AU - Naruishi, Koji
AU - Fattah, Elmoataz Abdel
AU - Aguilar-Cordova, Estuardo
AU - Butler, Edward Brian
AU - Thompson, Timothy C.
N1 - Funding Information:
Supported by Specialized Program of Research Excellence (SPORE) Grant P50-58204 from the National Cancer Institute, by the Methodist Hospital Foundation, and by the General Clinical Research Center.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR+CD8+ T cells were increased at all timepoints up to 8 months. The mean percentages of DR+CD4+ T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.
AB - Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR+CD8+ T cells were increased at all timepoints up to 8 months. The mean percentages of DR+CD4+ T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer.
KW - Gene therapy
KW - Hormonal therapy
KW - HSV-tk + VCV
KW - IMRT
KW - Prostate cancer
KW - Radiotherapy
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U2 - 10.1016/j.ijrobp.2005.11.009
DO - 10.1016/j.ijrobp.2005.11.009
M3 - Article
C2 - 16472937
AN - SCOPUS:33646009996
SN - 0360-3016
VL - 65
SP - 84
EP - 90
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -