Adoptive immunotherapy using bispecific antibody that blocks theEGFR signaling pathway

• Project/Area Number: 19790934
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: HIROKI Hayashi Tohoku University, 病院, 助教 (30422124)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,710,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 二重特異性抗体 / 上皮増殖因子受容体 / EGFR / 養子免疫療法

Research Abstract

We develop the bispecific antibody that binds both epidermal growth factor receptor (EGFR) and CD3 (lymphocyte's cell surface marker). This bispecific antibody greatly enhances lymphocyte's killer activity against cancer cells when administrated with lymphocytes. This effect is only observed against EGFR positive cancer cells (not against EGFR negative cells). This bispecific antibody seems very promising molecules against cancer immunotherapy because EGFR is widely expressing in many type of solid cancer. This effect was also observed in therapeutic models using mice.

Research Products

• [Journal Article] Target cell-restricted apoptosis induction by 528scFv-TRAIL fusion protein specific for human EGFR and expressed in Escherichia coli. (2010)
  • Author(s): Badran A, Asano R, Nakayama M, Watanabe Y, Nakanishi T, Umetsu M, Hayashi H, Katayose Y, Unno M, Kumagai I
  • Journal Title: Int J Oncol 36(5) Pages: 1229-34
  • Peer Reviewed
• [Journal Article] Application of the Fc fusion format to generate tag-free bi-specific diabodies. (2010)
  • Author(s): Asano R, Ikoma K, Kawaguchi H, Ishiyama Y, Nakanishi T, Umetsu M, Hayashi H, Katayose Y, Unno M, Kudo T, Kumagai I
  • Journal Title: FEBS J 277(2) Pages: 477-87
  • Peer Reviewed
• [Journal Article] Diabody-based recombinant formats of humanized IgG-like bispecific antibody with effective retargeting of lymphocytes to tumor cells. (2008)
  • Author(s): Asano R, Kawaguchi H, Watanabe Y, Nakanishi T, Umetsu M, Hayashi H, Katayose Y, Unno M, Kudo T, Kumagai I
  • Journal Title: J Immunother 31(8) Pages: 752-61
  • Peer Reviewed
• [Journal Article] Preferential heterodimerization of a bispecific diabody based on a humanized anti-EGFR antibody 528. (2008)
  • Author(s): Asano R, Sone Y, Ikoma K, Hayashi H, Nakanishi T, Umetsu M, Katayose Y, Unno M, Kudo T, Kumagai I
  • Journal Title: Protein Eng Des Sel 21(10) Pages: 597-603
  • Peer Reviewed
• [Journal Article] Highly effective recombinant format of a humanized IgG-like bispecific antibody for cancer immunotherapy with retargeting of lymphocytes to tumor cells. (2007)
  • Author(s): Asano R, Watanabe Y, Kawaguchi H, Fukazawa H, Nakanishi T, Umetsu M, Hayashi H, Katayose Y, Unno M, Kudo T, Kumagai I
  • Journal Title: J Biol Chem 282(38) Pages: 27659-65
  • Peer Reviewed
• [Presentation] GFRとCD3を標的とした新規ヒト型化二重特異性抗体の抗腫瘍効果の検討 (2009)
  • Author(s): 林洋毅、海野倫明:
  • Organizer: 第13回がん分子標的治療学会
  • Place of Presentation: 徳島
  • Year and Date: 2009-06-26
• [Presentation] EGFRとCD3を標的とした新規ヒト型化二重特異性抗体の抗腫瘍効果の検討 (2009)
  • Author(s): 林洋毅
  • Organizer: 第13回がん分子標的治療学会
  • Place of Presentation: ホテルクレメント徳島
  • Year and Date: 2009-06-26
• [Presentation] EGFR標的ヒト型化二重特異性抗体のセツキシマブとの比較検討. (2008)
  • Author(s): 渡部泰弘、林洋毅、浅野竜太郎、吉田寛、片寄友、安井寛、石田禎夫、江川新一、熊谷泉 、海野倫明
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-16