2011 Fiscal Year Final Research Report
Neoadjuvant in situ gene therapy with adenoviral delivery of HSV-tK gene for patients with high-risk prostate cancer
| Project/Area Number |
21592060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
BABA Shiro 北里大学, 医学部, 教授 (00051889)
MATSUMOTO Kazumasa 北里大学, 医学部, 講師 (70306603)
OKAYASU Isao 北里大学, 医学部, 教授 (20014342)
YANAGISAWA Nobuyuki 北里大学, 医学部, 講師 (80337914)
OBATA Fumiya 北里大学, 医療衛生学部, 教授 (60129236)
KUBU Makoto 北里大学, 医療衛生学部, 助教 (40464804)
TABATA Kenichi 北里大学, 医学部, 助教 (20327414)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 前立腺癌 / 遺伝子治療 / ネオアジュバント |
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| Research Abstract |
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.
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.
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).
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.
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Research Products
(14 results)
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[Presentation] Systemic T-cell activation following neoadjuvant in situ gene therapy in high-risk prostate cancer patients2012
Author(s)
Satoh T, Kubo M, Tabata K, Kurosaka S, Matsumoto K, Fujita T, Obata F, Nasu Y, Kumon H, Kadmon D, Brenner MK, Thompson TC, Baba S
Organizer
American Urological Association Annual Meeting
Place of Presentation
Atlanta, USA
Year and Date
2012-05-19
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[Presentation] ハイリスク前立腺癌に対するネオアジュバントHSV-tk遺伝子治療の検討2011
Author(s)
佐藤威文, 久保誠, 田畑健一, 黒坂眞二, 柳澤信之, 松本和将, 藤田哲夫, 佐藤絵里奈, 伊東一郎, 小幡文弥, 三枝信, 岡安勲, 那須保友, 公文裕巳, 馬場志郎
Organizer
第49回日本癌治療学会学術集会
Place of Presentation
名古屋
Year and Date
2011-10-27
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