Development of combination therapy with hyperthermia and targeted therapy

• Project/Area Number: 24792006
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Yokohama City University
• Principal Investigator: NAKASHIMA Hideyuki 横浜市立大学, 附属病院, 助教 (30437032)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 温熱療法 / 分子標的薬 / 併用療法 / 口腔癌 / 口腔扁平上皮癌

Research Abstract

Interleukin-13 receptor alpha 2 chain (IL-13Ra2), a unique tumor-associated antigen, is a promising target for cancer immunotherapy. IL13-PE, a targeted cytotoxin composed of IL-13 and mutated Pseudomonas exotoxin, induces specific killing of IL-13Ra2 positive tumor cells. Our objective is whether hyperthermia treatment of oral squamous cell carcinoma (OSCC) can modulate the expression of IL-13Ra2 and increase their sensitivity to IL13-PE.
OSCC cell lines, HSC-3 and SCC-25 cells were heated with 43 degree for 1 hour. The proliferation of heat-stressed OSCC cells showed more than 50% growth inhibition compared to control cells. IL-13Ra2 was up-regulated after heating of OSCC cells. Protein synthesis inhibition assay with IL13-PE showed that heat-stressed OSCC cells decreased the number of IC50 compared to that of without heated OSCC cells. The percentages of apoptotic cells increased in OSCC cells treated with IL13-PE after hyperthermia compared with controls.

Research Products

• [Journal Article] Targeting of interleukin-13 receptor α2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-β and PTEN signaling. (2013)
  • Author(s): Hall B, Nakashima H, Sun ZJ, Sato Y, Bian Y, Husain SR, Puri RK, Kulkarni AB.
  • Journal Title: J Transl Med. Volume: 11 Pages: 45-45
  • Peer Reviewed
• [Journal Article] Review: IL-13 receptor-directed cancer vaccines and immunotherapy. (2012)
  • Author(s): Nakashima H, Husain SR, Puri RK.
  • Journal Title: Immunotherapy Volume: 4 Issue: 4 Pages: 443-451
  • DOI: 10.2217/imt.12.28
  • Peer Reviewed
• [Presentation] A Combination therapy with hyperthermia and immunotoxin targeted IL-13 receptor alpha2 for human oral cancer cells (2014)
  • Author(s): M. Okubo, H. Nakashima, M. Kioi, T. Sakaguchi, H. Umemura, K. Sugiura, I. Sato, M. Iida, K. Mitsudo and I. Tohnai
  • Organizer: 第6回アジアハイパーサーミア腫瘍学会・第31回日本ハイパーサーミア学会合同大会
  • Place of Presentation: AOSSA （福井県）
• [Presentation] 口腔扁平上皮癌における分子標的薬と温熱療法との併用療法の開発. シンポジウム (2013)
  • Author(s): 中島 英行, 來生 知, 大久保牧子, 杉浦 圭, 佐藤 格, 飯田 昌樹, 佐藤 有紀, 光藤 健司, 藤内 祝
  • Organizer: 第30回日本ハイパーサーミア学会・学術大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-08-31
• [Presentation] 口腔扁平上皮癌における分子標的薬と温熱療法との併用療法の開発 (2013)
  • Author(s): 中島 英行，來生 知，大久保牧子，杉浦 圭，佐藤 格，飯田 昌樹，佐藤 有紀，光藤 健司，藤内 祝
  • Organizer: 第30回 日本ハイパーサーミア学会・学術大会
  • Place of Presentation: 横浜シンポジア（神奈川県）
  • Invited
• [Presentation] Interleukin-13 Receptor α2 chain Regulation in Human Head and Neck by Hyperthermia in vitro (2012)
  • Author(s): Sugiura K, Nakashima H, Okubo M, Sato I, Iida M, Sato Y, Kioi M, Mitsudo K, Husain SR, Tohnai, Puri RK
  • Organizer: International Conference on Diabetes Mellitus and Cancer (Dia-Can' 12)
  • Place of Presentation: Tamil Nadu, India
  • Year and Date: 2012-12-15
• [Presentation] A Novel Combination Immunotherapy for Targeting Murine Breast Cancer with IL-13 Receptor alpha 2 DNA Vaccine and an Immunotoxin (2012)
  • Author(s): Nakashima H, Husain SR, Sato Y. Kioi M. Tohnai I, Puri RK
  • Organizer: International Conference on Diabetes Mellitus and Cancer (Dia-Can' 12)
  • Place of Presentation: Tamil Nadu, India
  • Year and Date: 2012-12-15
• [Presentation] Hyperthermia sensitizes resistant human oral cancer cells to IL-13 cytotoxin (2012)
  • Author(s): Nakashima H, Kioi M, Okubo M, Sugiura K, Sato I, Iida M, Mitsudo K, Husain SR, Puri RK, Tohnai I
  • Organizer: ICHO & JCTM 2012 meeting
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2012-08-29
• [Presentation] Hyperthermia sensitizes resistant human oral cancer cells to IL-13 cytotoxin (2012)
  • Author(s): H. Nakashima, M. Kioi, M. Okubo, K. Sugiura, I. Sato, M. Iida, K. Mitsudo, S. R. Husain, R. K. Puri and I. Tohnai
  • Organizer: ICHO & JCTM 2012 meeting
  • Place of Presentation: ハイアットリージェンシー（京都府）
• [Presentation] Interleukin-13 Receptor α2 chain Regulation in Human Head and Neck by Hyperthermia in vitro (2012)
  • Author(s): Kei Sugiura, Hideyuki Nakashima, Makiko Okubo, Itaru Sato, Masaki. Iida, Yuki Sato, Mitomu Kioi, Kenji Mitsudo, Syed R. Husain, Iwai Tohnai and Raj K. Puri
  • Organizer: International Conference on Diabetes Mellitus and Cancer (Dia-Can’ 12)
  • Place of Presentation: Tamil Nadu, India
  • Invited