Dendritic cell-based immunotherapy for pediatric solid malignant tumor using the novel vector

• Project/Area Number: 18591955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Kyushu University
• Principal Investigator: TAJIRI Tatsuro Kyushu University, 医学研究院, 准教授 (80304806)
• Co-Investigator(Kenkyū-buntansha): TAGUCI Tomoaki 九州大学, 医学研究院, 教授 (20197247) ; SUEISHI Katsuo 九州大学, 医学研究院, 教授 (70108710) ; YONEMITSU Yoshikazu 千葉大学, 医学研究院, 客員教授 (40315065) ; KINOSHITA Yoshiaki 九州大学, 医学研究院, 助教講師 (80345529) ; 水田 祥代 九州大学, 大学病院, 教授 (30038856) ; 竜田 恭介 九州大学, 大学病院, 医員 (10380445)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,040,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥540,000); Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 小児腫瘍 / 免疫療法 / 遺伝子治療 / 樹状細胞 / センダイウィルスベクター / 神経芽腫 / センダイウィルス / 先天性横隔膜ヘルニア / 胎児治療 / 肺低形成 / 肺発達

Research Abstract

神経芽腫に対する外科療法と併用した樹状細胞治療の開発を目的に、前臨床試験としてマウス皮下担癌モデルにおいて、センダイウイルスベクター導入樹状細胞(SeV/DC)は有意に腫瘍増殖を抑制し、さらにSeVに搭載する遺伝子としてIFN-βを用いること、また放射線療法の併用療法で抗腫瘍効果が増強することを確認した。さらに、新たな知見として、放射線前照射によりSeV/DCが誘導する抗腫瘍免疫は、CTL活性を増強し長期メモリーを成立させることが分かった。また、抗腫瘍効果を担う主な免疫細胞は、原発巣の縮小にはCD4陽性T細胞が、再移植時にはCD8陽性T細胞が重要であることが示唆された。現在、臨床研究のプロトコールを作成中である。

Research Products

• [Journal Article] Complete Elimination of Established Neuroblastoma by Synergistic Action of g-Irradiation and DCs Treated with rSeV expressing Interferon-b Gene- (2009)
  • Author(s): Tatsuta K, Tanaka S, Tajiri T, Shibata S, Komaru A, Ueda Y, Inoue M, Hasegawa M, Suita S, Sueishi K, Taguchi T, and Yonemitsu Y
  • Journal Title: Gene Ther 16 Pages: 240-251
• [Journal Article] A preoperative evaluation for neo-infantile liver tumors using a three-dimensional reconstruction of multidetector row CT (2009)
  • Author(s): Kinoshita Y, Souzaki R , Tajiri T, Ieiri S, Taguchi T
  • Journal Title: Oncol Rep (in press)
• [Journal Article] A preoperative evaluation for neo-infantile liver tumors using a three-dimensional reconstruction of multidetector row CT. (2009)
  • Author(s): Kinoshita Y, Souzaki R, Tajiri T, et al.
  • Journal Title: Oncol Rep (in press)
  • Peer Reviewed
• [Journal Article] Complete Elimination of Established Neuroblastoma by Synergistic Action of g-Irradiation and DCs Treated with rSeV expressing Interferon-b Gene (2009)
  • Author(s): Tatsuta K, Tanaka S, Tajiri T, et al.
  • Journal Title: Gene Ther 16 Pages: 240-251
  • Peer Reviewed
• [Journal Article] Effectiveness of screening for neuroblastoma at 6 months of age : a retrospective population-based cohort study (2008)
  • Author(s): Hiyama E, Iehara T, Sugimoto T, Fukuzawa M, Hayashi Y, Sasaki F, Sugiyama M, Kondo S, Yoneda A, Yamaoka H, Tajiri T, Akazawa K, Ohtaki M.
  • Journal Title: Lancet 371 Pages: 1173-1180
• [Journal Article] Alterations of RB1 gene in embryonal and alveolar rhabdomyosarcoma : special reference to utility of Prb immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype (2008)
  • Author(s): Kohashi K, Oda Y, Yamamoto H, Tamiya S, Takahira T, Takahashi Y, Tajiri T, Taguchi T, Suita S, Tsuneyoshi M.
  • Journal Title: J Cancer Res Clin Oncol 30 Pages: 447-450
• [Journal Article] Transumbilical approach for neonatal surgical diseases-woundless operation- (2008)
  • Author(s): Tajiri T, Ieiri S, Kinoshita Y, Masumoto K, Nishimoto Y, Taguchi T
  • Journal Title: Pediatr Surg Int 24 Pages: 1123-1126
  • NAID: 10027864072
• [Journal Article] Clinical implications of a slight increase in the gene dosage of MYCN in neuroblastoma determined using quantitative PCR (2008)
  • Author(s): Souzaki R, Tajiri T, et al.
  • Journal Title: Pediatr Surg Int 24(10) Pages: 1095-1100
  • NAID: 10027863988
  • Peer Reviewed
• [Journal Article] Effectiveness of screening for neuroblastoma at 6 months of age : a retrospective population-based cohort study (2008)
  • Author(s): Hiyama E, Iehara T, Sugimoto T, Fukuzawa M, Hayashi Y, Sasaki F, Sugiyama M, Kondo S, Yoneda A, Yamaoka H, Tajiri T, et al.
  • Journal Title: Lancet 371 Pages: 1173-1180
  • Peer Reviewed
• [Journal Article] Diagnostic value of lectin reactive alpha-fetoprotein for neo-infantile hepatic tumors and malignant germ cell tumors-Preliminary study-. (2008)
  • Author(s): Kinoshita Y, Tajiri T, et al.
  • Journal Title: J Pediatr Hematol/Oncol 30 Pages: 447-450
  • Peer Reviewed
• [Journal Article] 進行神経芽腫治療に対する臓器温存手術と術後体外照射の意義 (2008)
  • Author(s): 田尻達郎, 宗崎良太, 木下義晶, 田中 桜, 田口智章
  • Journal Title: 小児外科 40 Pages: 624-628
  • Peer Reviewed
• [Journal Article] 生物学的予後因子解析からみたマススクリーニングの功罪 (2008)
  • Author(s): 田尻達郎, 宗崎良太, 木下義晶, 田中 桜, 東 真弓, 田口智章
  • Journal Title: 小児外科 40 Pages: 1047-1053
  • Peer Reviewed
• [Journal Article] Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy (2007)
  • Author(s): Suita S, Tajiri T, Kaneko M, Hirai M, Mugishima H, Sugimoto T, Tsuchida Y
  • Journal Title: J Pediatr Surg 42 Pages: 489-493
• [Journal Article] Insights into infant neuroblastomas based on an analysis of neuroblastomas detected by mass screening at 6 months of age in Japan (2007)
  • Author(s): Suita S, Tajiri T, Higashi M, Tanaka S, Kinoshita Y, Takahashi Y, Tatsuta K
  • Journal Title: Eur J Pediatr Surg 17 Pages: 23-28
• [Journal Article] Classification of neuroblastomas based on an analysis of the expression of genes related to the prognosis (2007)
  • Author(s): Tajiri T, Higashi M, Souzaki R, Tatsuta K, Kinoshita Y, Taguchi T
  • Journal Title: 42 Pages: 2046-2049
• [Journal Article] High expressions of neuronatin isoforms in favorable neuroblastoma (2007)
  • Author(s): Higashi M, Tajiri T, Kinoshita Y, Tatsuta K, Souzaki R, Maehara Y, Suita S, Taguchi T
  • Journal Title: J Pediatr Hematol/Oncol 29 Pages: 551-556
• [Journal Article] Risk factors for sensorineural hearing loss in survivors with severe congenital diaphragmatic hernia (2007)
  • Author(s): Masumoto K, et. al.
  • Journal Title: European Journal of Pediatrics 166 Pages: 607-612
  • Peer Reviewed
• [Journal Article] Clinical features selenium defiency in infants receiving long-term nutritional support (2007)
  • Author(s): Masumoto K, et. al.
  • Journal Title: Nutrition 23 Pages: 782-787
  • Peer Reviewed
• [Journal Article] Effectiveness of diaphragmatic repair using an abdominal muscle flap in patients with recurrent congenital diaphragmatic hernia (2007)
  • Author(s): Masumoto K, et. al.
  • Journal Title: Journal of Pediatric Surgery 42 Pages: 2007-2011
  • Peer Reviewed
• [Journal Article] Biological diagnosis for neuroblastoma using a highly sensitive analysis of prognostic factors (2006)
  • Author(s): Tajiri.T, Tanaka.S, Higashi.M, Kinoshita.Y, Takahashi.Y, Tatsuta.K, Suita.S
  • Journal Title: J Pediatr Surg 41 Pages: 560-566
• [Journal Article] Increased expression of c-fos and c-jun in the rat small intestinal epithelium after ischemia-reperfusion injury : a possible correlation with the proliferation or apoptosis of intestinal epithelial cells (2006)
  • Author(s): Shima.Y, Tajiri.T, Taguchi.T, Suita.S
  • Journal Title: J Pediatr Surg 41 Pages: 830-836
• [Journal Article] MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening (2006)
  • Author(s): Iehara.T, Hosoi.H, Akazawa.K, Matsumoto.Y, Yamamoto.K, Suita.S, Tajiri.T, Kusafuka.T, Hiyama.E, Kaneko.M, Sakai.F, Sugimoto.T, Sawada.T
  • Journal Title: Eur J Cancer 94 Pages: 1510-15
• [Journal Article] Clinical characteristics and outcome of Wilms tumors with a favorable histology in Japan : A report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan (2006)
  • Author(s): Suita.S, Kinoshita.Y, Tajiri.T, Hara.T, Tsuneyoshi.M, Mizote.H, Inada.H, Takamatsu.H, Kawano.Y, Inomata.Y, Nagasaki.A, Ono.Y, handa.N, Okamura.J, Ishii.E, Kawakami.K
  • Journal Title: J Pediatr Surg 41 Pages: 1501-1505
• [Journal Article] Association between Her2 expression and histological differentiation of Wilms tumor (2006)
  • Author(s): Salem.M, Kinoshita.Y, Tajiri.T, Souzaki.R, Tatsuta.K, Higashi.M, Izaki.T, Taguchi.T
  • Journal Title: Pediatr Surg Int 22 Pages: 891-896
• [Presentation] Dendritic cell-based immunotherapy with local radiation using Sendai virus vector for neuroblastoma (2008)
  • Author(s): Tatsuro Tajiri, Sakura Tanaka, Kyousuke Tatsuta, Yoshikazu Yonemitsu, Yasuji Ueda, and Tomoaki Taguchi
  • Organizer: 第67回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 小児固形悪性腫瘍に対する樹状細胞免疫遺伝子治療の開発 (2008)
  • Author(s): 田尻達郎, 米満吉和, 田中桜, 木下義晶, 宗崎良太, 田口智章
  • Organizer: 第8回九州がん懇話会
  • Place of Presentation: 福岡
  • Year and Date: 2008-09-20
• [Presentation] 小児固形悪性腫瘍に対する樹伏細胞免疫遺伝子治療の開発 (2008)
  • Author(s): 田尻達郎, 米満吉和, 田中桜, 木下義晶, 宗崎良太, 田口智章
  • Organizer: 第8回九州がん懇話会
  • Place of Presentation: 福岡
  • Year and Date: 2008-09-20
• [Presentation] 神経芽腫に対する 樹状細胞免疫遺伝子治療の開発 (2008)
  • Author(s): 田尻達郎, 米満吉和, 田中桜, 田口智章
  • Organizer: 第11回神経芽腫研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-23
• [Presentation] 神経芽腫に対する樹状細胞免疫遺伝子治療の開発 (2008)
  • Author(s): 田尻達郎, 米満吉和, 田中桜, 田口智章
  • Organizer: 第11回神経芽腫研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-23
• [Presentation] The implications of surgical intervention in the treatment of neuroblastomas (2008)
  • Author(s): Tajiri T, Kinoshita Y, Souzaki R, Tanaka S, Taguchi T
  • Organizer: 41^<th> Annual Meeting of Pacific Association of Pediatric Surgeons (PAPS), 2008
  • Place of Presentation: Wyoming, USA
  • Year and Date: 2008-06-30
• [Presentation] The implications of surgical intervention in the treatment of neuroblastomas. (2008)
  • Author(s): Tajiri T, Kinoshita Y, Souzaki R, Tanaka S, Taguchi T
  • Organizer: 41^<th> Annual Meeting of Pacific Association of Pediatric Surgeons (PAPS), 2008
  • Place of Presentation: Wyoming, USA
  • Year and Date: 2008-06-30
• [Presentation] センダイウイルスによる活性化樹状細胞を用いたマウス神経芽腫に対する抗腫瘍効果の検討-臨床応用に向けて (2008)
  • Author(s): 田中桜、田尻達郎、田口智章
  • Organizer: 第45回日本小児外科学会
  • Place of Presentation: つくば
  • Year and Date: 2008-05-29
• [Presentation] マスクリーニング休止後に発症した神経芽腫症例の臨床的・生物学的特性解析 (2008)
  • Author(s): 田尻達郎, 宗崎良太, 田中桜, 木下義晶, 古賀友紀, 住江愛子, 松崎彰信, 田口智章
  • Organizer: 第45回日本小児外科学会
  • Place of Presentation: つくば
  • Year and Date: 2008-05-29
• [Presentation] センダイウイルスによる活性化樹状細胞を用いたマウス神経芽腫に対する抗腫瘍効果の検討一臨床応用に向けて (2008)
  • Author(s): 田中桜, 田尻達郎, 田口智章
  • Organizer: 第45回日本小児外科学会
  • Place of Presentation: つくば
  • Year and Date: 2008-05-29
• [Presentation] Dendritic Cell-based Immunotherapy Using Sendai virus vector-a Preclinical Efficacy Study Against Neuroblastoma (2008)
  • Author(s): 田中桜, 田尻達郎, 田口智章
  • Organizer: 13th Advances in Neuroblastoma Research
  • Place of Presentation: 幕張
  • Year and Date: 2008-05-23
• [Presentation] The implications of surgical intervention in the treatment for neuroblastoma (2008)
  • Author(s): Tatsuro Tajiri, Yoshiaki Kinoshita, Ryota Souzaki, Sakura Tanaka, Tomoaki Taguchi
  • Organizer: 13th Advances in Neuroblastoma Research
  • Place of Presentation: 幕張
  • Year and Date: 2008-05-23
• [Presentation] Dendritic Cell-based Immunotherapy Using Sendai virus vector- a Preclinical Efficacy study Against Neuroblastoma - (2008)
  • Author(s): 田中桜, 田尻達郎, 田口智章
  • Organizer: 13th Advances in Neuroblastoma Research
  • Place of Presentation: 幕張
  • Year and Date: 2008-05-23
• [Presentation] 難治性小児固形悪性腫瘍に対する樹状細胞を用いた免疫治療の開発 (2008)
  • Author(s): 田尻達郎, 米満吉和, 田中桜, 竜田恭介, 木下義晶, 上田泰次, 水田祥代, 田口智章
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-15
• [Presentation] Effectiveness of diaphragmatic repair using an abdominal muscle flap in cases with recurrent congenital diaphragmatic hernia (2007)
  • Author(s): Masumoto K, et. al.
  • Organizer: 40th Annual Meeting of the Pacific Association of Pediatric Surgeons
  • Place of Presentation: Queenstown, New Zealand
  • Year and Date: 2007-04-18
• [Book] QOLを考えた小児外科疾患の治療 (2009)
  • Author(s): 田尻達郎
  • Publisher: 第19回地域医療研修センターテキスト
• [Book] 神経芽腫治療における外科治療の役割 (2008)
  • Author(s): 田尻達郎
  • Publisher: 第24回日本小児がん学会教育セッションテキスト
• [Book] 新臨床栄養学 (2007)
  • Author(s): 増本 幸二、水田 祥代
  • Publisher: 医学書院
• [Book] 専門性ゆえの多種多様な留学, 小児医療にみる医学留学へのパスポート (2006)
  • Author(s): 田尻達郎
  • Publisher: はる書房
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/pedsurg/