Complement-mediated immunotherapy to the Oral Squamous Cell Carcinoma with Cetuximab

• Project/Area Number: 23792148
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nagoya City University
• Principal Investigator: IMAI MASAKI 名古屋市立大学, 医学(系)研究科(研究院), 講師 (30440936)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 口腔癌 / 抗体 / 免疫療法

Research Abstract

To conserve both form and function in the oral area, effective and selective drugs against oral cancer will be required. We focused on Cetuximab, that is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing cancer. Complement deposition (C3) on HSC4 (human oral squamous cell carcinomas cell line) by incubation with Cetuximab and human serum was slightly enhanced. On the other hands, complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies. We investigated a strategy to amplify complement activation on tumor cells and overwhelm complement inhibitor function. Complement deposition and lysis of HSC4 cells by incubation with Cetuximab and human serum was enhanced in the presence of CR2-Fc. CR2-Fc enhances the therapeutic efficacy of antibody therapy and may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density.

Research Products

• [Journal Article] Complement C5A Antagonist Treatment Improves the Acute Circulatory and Inflammatory Consequences of Experimental Cardiac Tamponade (2013)
  • Author(s): Erces D, Nógrády M, Nagy E, Varga G, Vass A, Süveges G, Imai M, Okada N, Okada H, Boros M, Kaszaki J
  • Journal Title: Crit. Care. Med. Volume: 41 Issue: 11 Pages: e344-e351
  • DOI: 10.1097/ccm.0b013e31828a6768
  • Peer Reviewed
• [Journal Article] Anti-C5a complementary peptide ameliorates acute peritoneal injuries induced by neutralization of Crry and CD59. (2013)
  • Author(s): Mizuno T, Mizuno M, Imai M, Suzuki Y, Kushida M, Noda Y, Maruyama S, Okada H, Okada N, Matsuo S, Ito Y.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 305(11) Issue: 11 Pages: 1603-1616
  • DOI: 10.1152/ajprenal.00681.2012
  • Peer Reviewed
• [Journal Article] Inflammatory Activation after Experimental Cardiac Tamponade (2013)
  • Author(s): Vass A, Süveges G, Erces D, Nógrády M, Varga G, Földesi I, Futakuchi M, Imai M, Okada N, Okada H, Boros M, Kaszaki J
  • Journal Title: Eur Surg Res Volume: 51 Issue: 1-2 Pages: 1-13
  • DOI: 10.1159/000352089
  • Peer Reviewed
• [Journal Article] Interleukin-17A-Producing T Lymphocytes in Chronic Active Epstein-Barr Virus Infection. (2013)
  • Author(s): Ohta R
  • Journal Title: Microbiology and Immunology Volume: 57 Issue: 2 Pages: 139-144
  • DOI: 10.1111/1348-0421.12010
  • Peer Reviewed
• [Journal Article] Endothelin Receptor Antagonist Attenuates Oxidative Stress in Neonatal Sepsis Model. (2012)
  • Author(s): Goto T
  • Journal Title: Pediatric Research Volume: 72 Issue: 6 Pages: 600-605
  • DOI: 10.1038/pr.2012.134
  • Peer Reviewed
• [Journal Article] Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children (2011)
  • Author(s): Ito Y, Torii Y, Ohta R, Imai M, Hara S, Kawano Y, et al
  • Journal Title: Cytokine Volume: 56 Issue: 2 Pages: 180-187
  • DOI: 10.1016/j.cyto.2011.07.016
  • Peer Reviewed
• [Journal Article] Novel Complementary Peptides to Target Molecules (2011)
  • Author(s): Okada H, Imai M, Ono F, Okada A, Tada T, Mizue Y, Terao K, Okada N
  • Journal Title: Anticancer Res. Volume: 31 Pages: 2511-2516
  • URL: http://ar.iiarjournals.org/content/31/7/2511.long
  • Peer Reviewed
• [Journal Article] Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza (2011)
  • Author(s): Ohta R, Torii Y, Imai M, Kimura H, Okada N, Ito Y
  • Journal Title: Microbiol Immunol Volume: 55 Issue: 3 Pages: 191-198
  • DOI: 10.1111/j.1348-0421.2011.00309.x
  • NAID: 10031121459
  • Peer Reviewed
• [Journal Article] 腫瘍の補体制御膜因子による免疫回避 (2011)
  • Author(s): 今井優樹,岡田則子
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56 Pages: 31-37
  • URL: http://ci.nii.ac.jp/naid/40018938406
• [Journal Article] Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children. (2011)
  • Author(s): Ito Y, Torii Y, Ohta R, Imai M, Hara S, Kawano Y, Matsubayashi T, Inui A, Yoshikawa T, Nishimura N, Ozaki T, Morishima T, Kimura H
  • Journal Title: Cytokine Volume: 56 Pages: 180-187
  • Peer Reviewed
• [Journal Article] Novel Complementary Peptides to Target Molecules. (2011)
  • Author(s): Okada H, Imai M, Ono F, Okada A, Tada T, Mizue Y, Terao K, Okada N
  • Journal Title: Anticancer Research Volume: 31 Pages: 2511-2516
  • Peer Reviewed
• [Journal Article] Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza. (2011)
  • Author(s): Ohta R, Torii Y, Imai M, Kimura H, Okada N, Ito Y
  • Journal Title: Microbiology and Immunology Volume: 55 Pages: 191-198
  • NAID: 10031121459
  • Peer Reviewed
• [Presentation] Enhancement of anti-tumor immunity by MUC1-C3d fusion protein (2013)
  • Author(s): Imai M, Ohta R
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉市)
• [Presentation] ヒトにおけるMUC1-C3dワクチンのアジュバント効果の解析 (2013)
  • Author(s): 太田里永子,神田輝,安藤史代,今井優樹
  • Organizer: 第50回補体シンポジウム
  • Place of Presentation: 旭川医科大学(旭川)
• [Presentation] Enhancement of anti-tumor immunity by MUC1-C3d fusion protein. (2013)
  • Author(s): Imai M
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] Enhancing antibody immunotherapy by orally administered herbal medicine Juzen-taiho-to (2012)
  • Author(s): Imai M, Ohta R, Okada N
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場(神戸)
• [Presentation] C5a is a target to prevent peritoneal tissue damage in acute peritoneal injury in rats (2012)
  • Author(s): Mizuno T, Mizuno M, Imai M, Suzuki Y, Kushida M, Yamada K, Noda Y, Maruyama S, Okada H, Okada N, Matsuo S, Ito Y
  • Organizer: XXIV International Complement Workshop
  • Place of Presentation: Crete, Greece
• [Presentation] 口腔癌に対する抗MUC1モノクローナル抗体の抗腫瘍活性と補体膜制御因子の影響 (2012)
  • Author(s): 今井優樹,太田里永子、岡田則子
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪成人病センター(大阪)
• [Presentation] 急性腹膜生涯に対するアンチセンスC5aペプチドの治療効果 (2012)
  • Author(s): 水野智博,水野正司,櫛田真由,野田幸裕,山田清文,今井優樹,岡田秀親,岡田則子,丸山彰一,松尾清一,伊藤恭彦
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪成人病センター(大阪)
• [Presentation] C5a is a target to prevent peritoneal tissue damage in acute peritoneal injury in rats. (2012)
  • Author(s): Mizuno T
  • Organizer: XXIV International Complement Workshop
  • Place of Presentation: Minoa Palace Conference Center (Crete, Greece)
• [Presentation] Enhancing antibody immunotherapy by orally administered herbal medicine Juzen-taiho-to. (2012)
  • Author(s): Imai M
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場(兵庫県)
• [Presentation] 口腔癌に対する抗MUC1モノクローナル抗体の抗腫瘍活性と補体膜制御因子の影響 (2012)
  • Author(s): 今井優樹
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪府立成人病センター(大阪府）
• [Presentation] 第49回補体シンポジウム (2012)
  • Author(s): 水野智博
  • Organizer: 第49回補体シンポジウム
  • Place of Presentation: 大阪府立成人病センター(大阪府）
• [Presentation] Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza (2011)
  • Author(s): Imai M, Ohta R, Okada N
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
• [Presentation] Inactivation of C5a anaphylatoxin is an effective treatment of sepsis (2011)
  • Author(s): Okada N, Imai M, Goto T, Hamed M, Okada A, Ono F, Okada H
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
• [Presentation] H1N1インフルエンザの重症化における補体アナフィラトキシン及びHMGB1の関与 (2011)
  • Author(s): 太田里永子,伊藤嘉規,鳥居ゆか,木村宏,岡田則子,今井優樹
  • Organizer: 第48回補体シンポジウム
  • Place of Presentation: 名古屋市立大学(愛知県)
• [Presentation] Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza (2011)
  • Author(s): Imai M, Ohta R, Okada N,
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] Inactivation of C5a anaphylatoxin is an effective treatment of sepsis. (2011)
  • Author(s): Okada N, Imai M, Goto T, Hamed M, Okada A, Ono F, Okada H
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉県）
• [Presentation] H1N1 インフルエンザの重症化における補体アナフィラトキシン及びHMGB1 の関与. (2011)
  • Author(s): 太田里永子, 伊藤嘉規, 鳥居ゆか, 木村宏, 岡田則子, 今井優樹
  • Organizer: 第4 8 回補体シンポジウム
  • Place of Presentation: 名古屋市立大学(愛知県)
• [Presentation] プロカルボキシペプチダーゼR 欠損はコンカナバリンA 誘発性肝炎による致死率を雌マウスにおいて増大させる. (2011)
  • Author(s): 朝井鈴佳、金原紀章、多田豊廣、今井優樹、Campbell W, 岡田秀親、岡田則子
  • Organizer: 第4 8 回補体シンポジウム
  • Place of Presentation: 名古屋市立大学(愛知県）
• [Presentation] 急性腹膜障害に対するC5a の関与とC5a 阻害薬の有用性 (2011)
  • Author(s): 水野智博, 水野正司, 櫛田真由, 野田幸裕, 山田清文, 今井優樹, 岡田秀親, 岡田則子, 丸山彰一, 松尾清一, 伊藤恭彦
  • Organizer: 第4 8 回補体シンポジウム
  • Place of Presentation: 名古屋市立大学(愛知県)
• [Book] 補体への招待 (2011)
  • Author(s): 今井優樹, 岡田則子 他
  • Total Pages: 231
  • Publisher: メジカルビュー社