The new cancer therapy of cetuximab through ADCC activity by NK cells

• Project/Area Number: 15K11276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kanagawa Dental College
• Principal Investigator: OZAWA SHIGEYUKI 神奈川歯科大学, 大学院歯学研究科, 講師 (40434394)
• Co-Investigator(Kenkyū-buntansha): 近藤 忠稚 神奈川歯科大学, 歯学部, 非常勤講師 (00587727) ; 前畑 洋次郎 神奈川歯科大学, 大学院歯学研究科, 特任講師 (80410009)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: CXCL14 / ADCC / 頭頚部扁平上皮癌 / セツキシマブ / 頭頸部癌

Outline of Final Research Achievements

To examine whether NK cells are involved in cetuximab’s antitumor effect, we removed NK cells from mice using anti‐asialo GM1 antibody (antibody that recognizes the glycolipid asialo GM1 expressed on the cell membrane of NK cells) and investigated the results. Although cetuximab tended to have a weaker effect in the group without NK cells, there was no clear significant difference. We investigated the correlation between cetuximab and ADCC activity using an ADCC measurement kit, but we were unable to detect cetuximab-induced ADCC activity in the cell lines we used. We think that perhaps the cancer cells we used had low levels of EGFR expression, which meant we were unable to detect sufficient levels of ADCC activity. Based on the above information, we feel it is essential to use cancer cells with high levels of EGFR expression for future research on ADCC activity.

Research Products

• [Journal Article] Expression of the chemokine CXCL14 and cetuximab-dependent tumour suppression in head and neck squamous cell carcinoma. (2016)
  • Author(s): Kondo T, Ozawa S, Ikoma T1, Yang XY, Kanamori K, Suzuki K, Iwabuchi H, Maehata Y, Miyamoto C, Taguchi T, Kiyono T, Kubota E, Hata RI
  • Journal Title: Oncogenesis Volume: 5 Issue: 7 Pages: 1-10
  • DOI: 10.1038/oncsis.2016.43
  • Peer Reviewed / Open Access
• [Journal Article] Chemokine CXCL14 is a multistep tumor suppressor. (2016)
  • Author(s): Yang X Y, Miyamoto C, Akasaka T, Izukuri K, Maehata Y, Ikoma T, Ozawa S, Hata R.
  • Journal Title: Journal of Oral Biosciences Volume: 58 Pages: 16-22
  • Peer Reviewed
• [Presentation] エピジェネティクス異常が及ぼす頭頚部扁平上皮癌のセツキシマブ抵抗性の検討 (2017)
  • Author(s): 金森慶亮
  • Organizer: 日本口腔外科学会総会
• [Presentation] CXCL14は上皮成長因子受容体 (EGFR) 阻害剤投与前のマーカーとなりうる (2017)
  • Author(s): 小澤重幸
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Expression of the chemokine CXCL14 is a predictive biomarker for cetuximab-dependent tumor suppression. (2016)
  • Author(s): Yang X-Y, Ozawa S, Ikoma T, Suzuki K, Kanamori K, Kiyono T, Kubota E, Hata R-I.
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] 多段階癌抑制 分子のケモカインCXCL14/BRAKは扁平上皮の分化制御因子か？ (2016)
  • Author(s): 生駒丈晴, 陽暁艶, 小澤重幸, 前畑洋次郎, 畑隆一郎
  • Organizer: 第58回歯科基礎医学会学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-06-24
• [Presentation] ケモカインCXCL14の発現がセツキシマブ(抗上皮増殖因子受容体抗体)による腫瘍抑制活性を決定する. (2016)
  • Author(s): 陽暁艶, 近藤忠稚, 小澤重幸,生駒丈晴, 鈴木健司, 岩淵博史, 前畑洋次郎,宮本千央, 久保田英朗, 畑隆一郎
  • Organizer: 第48回日本結合組織学会学術大会
  • Place of Presentation: 長崎
  • Year and Date: 2016-06-24
• [Presentation] Expression of the chemokine CXCL14 is a predictive biomarker for Cetuximab-dependent tumour supression (2015)
  • Author(s): 生駒丈晴
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-09-11