Application of in-house monoclonal antibody resources to a fully retargeted oncolytic herpes simplex virus platform

• Project/Area Number: 23800058
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Clinical oncology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: UCHIDA Hiroaki 東京薬科大学, 生命科学部, 准教授 (20401250)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 遺伝子治療 / 癌 / 腫瘍溶解ウイルス療法 / 単純ヘルペスウイルス / 抗体医薬 / がん / ヘルペスウイルス / 癌標的化治療

Research Abstract

We have reported a fully retargeted herpes simplex virus (HSV) platform that incorporates single-chain antibodies to mediate virus entry exclusively via tumor-associated antigens. For further development of this system, we successfully took advantage of our own collection of monoclonal antibodies directed against human cancers. Our results indicate the adaptability of our system to different targeting ligands, leading to a new generation of broadly applicable and effective oncolytic HSV vectors.

Research Products

• [Journal Article] Effective treatment of an orthotopic xenograft model of human glioblastoma using an EGFR-retargeted oncolytic herpes simplex virus (2013)
  • Author(s): Uchida H, Marzulli M, Nakano K, Goins WF, Chan J, Hong CH, Mazzacurati L, Yoo JY, Haseley A, Nakashima H, Baek H, Kwon H, Kumagai I, Kuroki M, Kaur B, Chiocca EA, Grandi P, Cohen JB, Glorioso JC
  • Journal Title: Mol Ther Volume: 21(3) Pages: 561-9
• [Journal Article] Novel mutations in gB and gH circumvent the requirement for known gD receptors in HSV-1 entry and cell-to-cell spread (2013)
  • Author(s): Uchida H, Chan J, Shrivastava I, Reinhart B, Grandi P, Glorioso JC, Cohen JB
  • Journal Title: J Virol Volume: 87(3) Pages: 1430-42
• [Journal Article] Bispecific adapter-mediated retargeting of a receptor-restricted HSV-1 vector to CEA-bearing tumor cells (2011)
  • Author(s): Baek H, Uchida H, Jun K, Kim JH, Kuroki M, Cohen JB, Glorioso JC, Kwon H
  • Journal Title: Mol Ther Volume: 19(3) Issue: 3 Pages: 507-14
  • DOI: 10.1038/mt.2010.207
  • Peer Reviewed
• [Journal Article] Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV
  • Author(s): Wang PY, Currier MA, Hansford L, Kaplan D, Chiocca EA, Uchida H, Goins WF, Cohen JB, Glorioso JC, Kuppevelt TH, Mo X, Cripe TP
  • Journal Title: Gene Ther Volume: (in press)
• [Presentation] 高性能癌標的化抗体の網羅的探索と標的化ヘルペスウイルスベクター系の完成 (2012)
  • Author(s): 内田宏昭
  • Organizer: バイオテック2012アカデミックフォーラム
  • Place of Presentation: 東京
• [Presentation] 標的化ヘルペスウイルスでがんを狙い撃ち-エンベロープ糖タンパクの遺伝子工学的改変 (2012)
  • Author(s): 内田宏昭、濱田洋文、Justus B. Cohen、Joseph C. Glorioso
  • Organizer: 第2回医薬工3大学包括連携推進シンポジウム
  • Place of Presentation: 東京
• [Presentation] 単純ヘルペスウイルスのターゲティング-2種類のウイルス糖タンパクの同時改変 (2011)
  • Author(s): 内田宏昭, 中野賢二, Chang-Sook Hong, William Goins, Janet Chan, Heechung Kwon, 熊谷泉, 黒木政秀, Justus Cohen, Joseph Glorioso
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Fully retargeted herpes simplex virus vector by co-engineering of viral glycoproteins (2011)
  • Author(s): Uchida, H
  • Organizer: The 17th Annual Meeting of Japan Society of Gene Therapy
  • Place of Presentation: Hakata, Japan
• [Presentation] 腫瘍細胞のみに感染可能な標的化ヘルペスウイルスベクターの実現 (2011)
  • Author(s): 内田宏昭, Justus Cohen, Joseph Glorioso
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京
• [Presentation] 腫瘍細胞のみに感染可能な標的化ヘルペスウイルスベクターの実現 (2011)
  • Author(s): 内田宏昭, Justus Cohen, Joseph Glorioso
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京(紙上開催)
• [Presentation] Fully retargeted herpes simplex virus vector by co-engineering of viral glycoproteins (2011)
  • Author(s): Uchida H
  • Organizer: The 17th Annual Meeting of the Japan Society of Gene Therapy
  • Place of Presentation: Fukuoka, Japan
• [Remarks]
  • URL: http://logos.ls.toyaku.ac.jp/~shuyouken/onclab-J/OnclabHP.html