Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients.
OBJECTIVE
To explore long-term immune responses after combined radio-gene-hormonal therapy.


METHODS
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.
Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
Tetsuo
T
Fujita
Bin S
BS
Teh
Terry L
TL
Timme
Wei-Yuan
WY
Mai
Takefumi
T
Satoh
Nobuyuki
N
Kusaka
Koji
K
Naruishi
Elmoataz Abdel
EA
Fattah
Estuardo
E
Aguilar-Cordova
E Brian
EB
Butler
Timothy C
TC
Thompson
D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000532:radiotherapy / Q000628:therapy*; D050397:Radiotherapy, Intensity-Modulated; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000235:genetics; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000726:Androgen Antagonists; D000998:Antiviral Agents; D013937:Thymidine Kinase; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir