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.
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.
Authors: Nathan VanderVeen; Christopher Paran; Jonathan Krasinkiewicz; Lili Zhao; Donna Palmer; Shawn Hervey-Jumper; Philip Ng; Pedro R Lowenstein; Maria G Castro Journal: Hum Gene Ther Clin Dev Date: 2013-09 Impact factor: 5.032
Authors: E Antonio Chiocca; Laura K Aguilar; Susan D Bell; Balveen Kaur; Jayson Hardcastle; Robert Cavaliere; John McGregor; Simon Lo; Abhik Ray-Chaudhuri; Arnab Chakravarti; John Grecula; Herbert Newton; Kimbra S Harris; Robert G Grossman; Todd W Trask; David S Baskin; Carissa Monterroso; Andrea G Manzanera; Estuardo Aguilar-Cordova; Pamela Z New Journal: J Clin Oncol Date: 2011-08-15 Impact factor: 44.544
Authors: Steven Eric Finkelstein; Francisco Rodriguez; Mary Dunn; Mary-Jane Farmello; Renee Smilee; William Janssen; Loveleen Kang; Tian Chuang; John Seigne; Julio Pow-Sang; Javier F Torres-Roca; Randy Heysek; Matt Biagoli; Ravi Shankar; Jacob Scott; Scott Antonia; Dmitry Gabrilovich; Mayer Fishman Journal: Immunotherapy Date: 2012-04 Impact factor: 4.196