790 SYSTEMIC T-CELL ACTIVATION FOLLOWING NEOADJUVANT IN SITU GENE THERAPY IN HIGH-RISK PROSTATE CANCER PATIENTS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2012790 SYSTEMIC T-CELL ACTIVATION FOLLOWING NEOADJUVANT IN SITU GENE THERAPY IN HIGH-RISK PROSTATE CANCER PATIENTS Takefumi Satoh, Makoto Kubo, Ken-ichi Tabata, Shinji Kurosaka, Kazumasa Matsumoto, Tetsuo Fujita, Fumiya Obata, Yasutomo Nasu, Hiromi Kumon, Dov Kadmon, Malcolm K. Brenner, Timothy C. Thompson, and Shiro Baba Takefumi SatohTakefumi Satoh Kanagawa, Japan More articles by this author , Makoto KuboMakoto Kubo Kanagawa, Japan More articles by this author , Ken-ichi TabataKen-ichi Tabata Kanagawa, Japan More articles by this author , Shinji KurosakaShinji Kurosaka Kanagawa, Japan More articles by this author , Kazumasa MatsumotoKazumasa Matsumoto Kanagawa, Japan More articles by this author , Tetsuo FujitaTetsuo Fujita Kanagawa, Japan More articles by this author , Fumiya ObataFumiya Obata Kanagawa, Japan More articles by this author , Yasutomo NasuYasutomo Nasu Okayama, Japan More articles by this author , Hiromi KumonHiromi Kumon Okayama, Japan More articles by this author , Dov KadmonDov Kadmon Houston, TX More articles by this author , Malcolm K. BrennerMalcolm K. Brenner Houston, TX More articles by this author , Timothy C. ThompsonTimothy C. Thompson Houston, TX More articles by this author , and Shiro BabaShiro Baba Kanagawa, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.878AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Neoadjuvant in situ cytotoxic gene therapy can potentially trigger a systemic immune response, which could impact occult micro-metastatic disease. We are currently conducting adenoviral vector mediated Herpes Simplex Virus-thymidine kinese (HSV-tk) gene plus ganciclovir (GCV) therapy as neoadjuvant intraprostatic injection for localized high-risk prostate cancer. This study evaluates the systemic T-cell response following gene therapy. METHODS We enrolled 5 men with clinically localized prostate cancer but high risk for recurrence (Kattan nomogram score > 115) in this Phase I–II trial. Intraprostatic viral injections (two) were followed by 2 weeks of GCV and prostatectomy 4 weeks later. Peripheral blood lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Samples were taken at the time of HSV-tk virus injection and at selected intervals afterwards. 100 μl of heparin-treated blood was incubated with dual color labeled antibody pairs: CD45/CD14, CD3/CD19, CD3/CD8, CD3/CD4, CD8/HLA-DR, CD4/HLA-DR, CD3/HLA-DR, CD3/CD56+CD16 and CD4/CD25. Forward and side scatter was set to distinguish lymphocyte, macrophage, and granulocyte populations with an EPICS XL flow cytometer. RESULTS A reduction in serum PSA was observed immediately after vector injection and GCV therapy in all patients. The mean reduction was 31.1% and ranged from 24.8 to 38.9%. The pretreatment mean percentage of CD8+ T cells positive for the HLA-DR marker of activation was 10.6%. For day 2, day 7, day 14, day 16 and day 56 post treatment, the mean percent of CD8+ DR+ T cells increased by 14.0%, 12.3%, 19.7%, 25.4% and 14.9%, which were statistically significant (day 14; p = 0.0431, day 16; p = 0.0431). CONCLUSIONS We present evidence of systemic T-cell responses following HSV-tk + GCV gene therapy under clinical trial condition. There was an increase in activated CD8+ T cells in the peripheral blood following vector injection suggesting the potential for activation of components of cell-mediated immune response in this neoadjuvant setting. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e323 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takefumi Satoh Kanagawa, Japan More articles by this author Makoto Kubo Kanagawa, Japan More articles by this author Ken-ichi Tabata Kanagawa, Japan More articles by this author Shinji Kurosaka Kanagawa, Japan More articles by this author Kazumasa Matsumoto Kanagawa, Japan More articles by this author Tetsuo Fujita Kanagawa, Japan More articles by this author Fumiya Obata Kanagawa, Japan More articles by this author Yasutomo Nasu Okayama, Japan More articles by this author Hiromi Kumon Okayama, Japan More articles by this author Dov Kadmon Houston, TX More articles by this author Malcolm K. Brenner Houston, TX More articles by this author Timothy C. Thompson Houston, TX More articles by this author Shiro Baba Kanagawa, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...