Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

Tetsuo Fujita, Bin S. Teh, Terry L. Timme, Wei Yuan Mai, Takefumi Satoh, Nobuyuki Kusaka, Koji Naruishi, Elmoataz Abdel Fattah, Estuardo Aguilar-Cordova, Edward Brian Butler, Timothy C. Thompson

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)84-90
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume65
Issue number1
DOIs
StatePublished - May 1 2006

Keywords

  • Gene therapy
  • Hormonal therapy
  • HSV-tk + VCV
  • IMRT
  • Prostate cancer
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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