Use of combination of frozen tumor tissue and dendritic cell immunotherapy

• Project/Area Number: 25293318
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kanazawa University
• Principal Investigator: Nishida Hideji 金沢大学, 医学系, 協力研究員 (50569374)
• Co-Investigator(Kenkyū-buntansha): Miwa Shinji 金沢大学, 大学病院, 医員 (40753455)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000); Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: 骨腫瘍 / 軟部腫瘍 / 樹状細胞 / 免疫療法 / 骨軟部肉腫 / TNFα / 骨軟部腫瘍に対する樹状細胞療法

Outline of Final Research Achievements

Thirty seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing IL-4 and GM-CSF. These cells were treated with tumor lysate, TNF-α, and OK-432. One treatment course comprised weekly DC injection for 6 times. Toxicity, clinical response (tumor volume, serum IFN-γ, and serum IL-12), and oncological outcomes were observed. DC therapy were performed in 37 patients. No severe adverse event and death associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 were observed 1 month after DC injection. 6 cases had stable disease, and 1 case showed partial response 3 months after DC therapy. Of the 37 patients, 13 patients were alive and 1 patient was progression free at the time of the final follow-up. Overall survival rates and progression free survival rates of the patients at 3 years were 42.3% and 2.9%, respectively.

Research Products

• [Journal Article] Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report. (2015)
  • Author(s): Takeuchi A, Yamamoto N, Shirai T, Nishida H, Hayashi K, Watanabe K, Miwa S, Tsuchiya H.
  • Journal Title: BMC Surgery Volume: 15 Pages: 124-124
  • DOI: 10.1186/s12893-015-0112-3
  • Peer Reviewed / Open Access
• [Journal Article] Frozen Autograft-Prosthesis Composite Reconstruction in Malignant Bone Tumors. (2015)
  • Author(s): Subhadrabandhu S, Takeuchi A, Yamamoto N, Shirai T, Nishida H, Hayashi K, Miwa S, Tsuchiya H.
  • Journal Title: Orthopedics Volume: 38
  • DOI: 10.3928/01477447-20151002-59
  • Peer Reviewed
• [Journal Article] Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy. (2015)
  • Author(s): Hayashi K, Yamada S, Inatani H, Okamoto H, Takeuchi A, Nishida H, Yamamoto N, Tsuchiya H, Otsuka T
  • Journal Title: Anticancer Research Volume: 35 Pages: 493-8
  • Peer Reviewed
• [Journal Article] Heterogeneous cell-cycle behavior in response to UVB irradiation by a population of single cancer cells visualized by time-lapse FUCCI imaging. (2015)
  • Author(s): Miwa S, Yano S, Kimura H, Yamamoto M, Toneri M, Murakami T, Hayashi K, Yamamoto N, Fujiwara T, Tsuchiya H, Hoffman RM.
  • Journal Title: Cell Cycle Volume: 14 Pages: 1932-1937
  • DOI: 10.1080/15384101.2015.1033598
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging. (2015)
  • Author(s): Miwa S, Yano S, Kimura H, Yamamoto M, Toneri M, Matsumoto Y, Uehara F, Hiroshima Y, Murakami T, Hayashi K, Yamamoto N, Bouvet M, Fujiwara T, Tsuchiya H, Hoffman RM.
  • Journal Title: Cell Cycle Volume: 14 Pages: 621-629
  • DOI: 10.4161/15384101.2014.991604
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Salvage method for unplanned excision of soft tissue sarcoma: long-term results of second-look surgery following radio-hyperthermo-chemotherapy. (2015)
  • Author(s): Hayashi K, Yamada S, Inatani H, Okamoto H, Takeuchi A, Nishida H, Yamamoto N, Tsuchiya H, Otsuka T.
  • Journal Title: Anticancer Res Volume: 35 Pages: 493-8
  • Peer Reviewed
• [Journal Article] Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study. (2015)
  • Author(s): Kimura H, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Takeuchi A, Igarashi K, Inatani H, Shimozaki S, Kato T, Aoki Y, Higuchi T, Tsuchiya H.
  • Journal Title: Cancer Med Volume: 4 Pages: 333-341
  • DOI: 10.1002/cam4.373
  • Peer Reviewed / Open Access
• [Journal Article] Late recurrence of osteosarcoma: a report of two cases. (2014)
  • Author(s): Igarashi K, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Miwa S, Inatani H, Shimozaki S, Kato T, Tsuchiya H.
  • Journal Title: J Orthop Surg (Hong Kong) Volume: 22 Pages: 415-9
  • Peer Reviewed / Open Access
• [Journal Article] Outcomes and complications of reconstruction using tumor-bearing frozen autografts in patients with metastatic bone tumors. (2014)
  • Author(s): Miwa S, Takeuchi A, Shirai T, Yamamoto N, Hayashi K, Nishida H, Kimura H, Igarashi K, Tsuchiya H.
  • Journal Title: Anticancer Res Volume: 34 Pages: 5569-77
  • Peer Reviewed
• [Journal Article] Synovial sarcoma in knee joint, mimicking low-grade sarcoma confirmed by molecular detection of SYT gene split. (2014)
  • Author(s): Kimura H, Yamamoto N, Nishida H, Hayashi K, Takeuchi A, Nojima T, Ikeda H, Sawada-Kitamura S, Tsuchiya H.
  • Journal Title: Anticancer Res Volume: 34 Pages: 3105-11
• [Journal Article] Antimicrobial megaprostheses supported with iodine. (2014)
  • Author(s): Shirai T, Tsuchiya H, Nishida H, Yamamoto N, Watanabe K, Nakase J, Terauchi R, Arai Y, Fujiwara H, Kubo T.
  • Journal Title: J Biomater Appl Volume: 29 Pages: 617-23
  • DOI: 10.1177/0885328214539365
  • Peer Reviewed
• [Journal Article] Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities (2014)
  • Author(s): Shimozaki S, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Kimura H, Takeuchi A, Igarashi K, Inatani H, Kato T, Tsuchiya H
  • Journal Title: J Orthop Sci. Volume: 19(1) Pages: 156-163
  • DOI: 10.1007/s00776-013-0487-x
  • NAID: 120005349170
  • Peer Reviewed
• [Journal Article] Diagnosis and treatment of low-grade osteosarcoma : experience with nine cases (2014)
  • Author(s): Hayashi K, Tsuchiya H, Yamamoto N, Shirai T, Nishida H, Takeuchi A, Kimura H, Miwa S, Inatani H, Okamoto H, Yamada S, Ikeda H, Sawada-Kitamura S, Nojima T, Ooi A, Otsuka T
  • Journal Title: Int J Clin Oncol Volume: Jul 24 Pages: 731-8
  • DOI: 10.1007/s10147-013-0592-z
  • Peer Reviewed
• [Presentation] Clinical outcomes and complications of reconstruction using tumor-bearing frozen autografts in patients with metastatic bone tumors (2015)
  • Author(s): Shinji Miwa, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Hiroyuki Inatani, Yu Aoki, Takashi Higuchi, Kensaku Abe, Hiroyuki Tsuchiya
  • Organizer: 第42回日本低温医学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-11-26
• [Presentation] 骨肉腫の術前化学療法後の画像変化と予後の相関についての検討 (2015)
  • Author(s): 三輪真嗣，山本憲男，林克洋，武内章彦，稲谷弘幸，青木裕，樋口貴史，阿部健作，土屋弘行
  • Organizer: 第48 回 日本整形外科学会骨・軟部腫瘍学術集会
  • Place of Presentation: 香川
  • Year and Date: 2015-07-09
• [Presentation] 骨肉腫マウスモデルに対する蛍光ガイド下手術の検討 (2015)
  • Author(s): 三輪真嗣，上原史成，木村浩明，林克洋，山本憲男，Robert M. Hoffman，土屋弘行
  • Organizer: 第88回日本整形外科学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-05-21
• [Presentation] 悪性骨軟部腫瘍に対する免疫療法（樹状細胞療法）の可能性 (2014)
  • Author(s): 西田英司、山本憲男、林克洋、武内章彦、下崎真吾、加藤貴士、樋口貴史、青木裕、土屋 弘行
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 城山観光ホテル（鹿児島県鹿児島市）
  • Year and Date: 2014-11-09 – 2014-11-10
• [Presentation] 悪性骨軟部腫瘍に対する腫瘍破砕物質を抗原としTNF-αを併用した樹状細胞を用いた免疫療法 (2014)
  • Author(s): 西田英司、山本憲男、武内章彦、木村浩明、野村一世、土屋弘行
  • Organizer: 第５２回日本癌治療学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] 標準治療抵抗性の悪性骨・軟部腫瘍に対する樹状細胞療法の可能性 (2014)
  • Author(s): 西田英司、山本憲男、白井寿治、林克洋、武内章彦、丹沢義一、木村浩明、三輪真嗣、五十嵐健太郎、下崎真吾、加藤貴士、青木裕、樋口貴史、土屋弘行
  • Organizer: 第４７回日本整形外科学会 骨・軟部腫瘍学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-07-17 – 2014-07-18
• [Presentation] Immunotherapy based on dendritic cells is feasible for patients with malignant bone and soft tissue tumours (2014)
  • Author(s): Hideji Nishida, Norio Yamamoto, Toshiharu Shirai, Katsuhiro Hayashi, Akihiko Takeuchi, Yoshikazu Tanzawa, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Hiroyuki Tsuchiya
  • Organizer: 2014 American Society of Clinical Oncology
  • Place of Presentation: MaCormick Place (Chicago, Ilinois)
  • Year and Date: 2014-05-30 – 2014-06-04
• [Presentation] Dendritic cells immunotherapy for patients with malignant bone and soft tissue tumours (2014)
  • Author(s): Hideji Nishida, Norio Yamamoto, Toshiharu Shirai, Katsuhiro Hayashi, Akihiko Takeuchi, Yoshikazu Tanzawa, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Hiroyuki Tsuchiya
  • Organizer: 第86回 日本整形外科学会総会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2014-05-22 – 2014-05-25
• [Presentation] 悪性骨軟部腫瘍に対する腫瘍破砕物質を抗原としTNF-αを併用した樹状細胞を用いた免疫療法 (2013)
  • Author(s): 西田英司、山本憲男、武内章彦、木村浩明、野村一世、土屋弘行
  • Organizer: 第１２０回中部日本整形外科災害外科学会
  • Place of Presentation: 和歌山 和歌山県民文化会館・ホテルアバローム紀の国
• [Presentation] Immunotherapy based on dendritic cells is feasible for patients with malignant bone and soft tissue tumours (2013)
  • Author(s): Hideji Nishida, Norio Yamamoto, Akihiko Takeuchi, Yoshikazu Tanzawa, Hiroaki Kimura, Munetomo Takata, Isei Nomura, Shinji Miwa, Takashi Kato, Hiroyuki Tsuchiya
  • Organizer: 26th European Musculoskeletal Oncology Society Meeting
  • Place of Presentation: ヨーテボリ、スウェーデンSwedish Exhibition and Congress Center
• [Presentation] Immunotherapy based on dendritic cells is feasible for patients with malignant bone and soft tissue tumours (2013)
  • Author(s): Hideji Nishida, Norio Yamamoto, Toshiharu Shirai, Katsuhiro Hayashi, Akihiko Takeuchi, Yoshikazu Tanzawa, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Hiroyuki Tsuchiya
  • Organizer: International Society of Limb Salvage 17th General Meeting
  • Place of Presentation: ボローニャ、イタリア