Immune-biomarkers for evaluation of clinical activity of VEGFR-targeted vaccines against malignant glioma patients

• Project/Area Number: 24592172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Keio University
• Principal Investigator: UEDA RYO 慶應義塾大学, 医学部, 共同研究員 (30317143)
• Co-Investigator(Renkei-kenkyūsha): TODA Masahiro 慶應義塾大学, 医学部, 准教授 (20217508)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 悪性神経膠腫 / がんペプチドワクチン / 抗腫瘍免疫 / 腫瘍血管新生 / 脳腫瘍 / ペプチドワクチン / 免疫療法

Outline of Final Research Achievements

Immune-biomarkers and -assays are important for development of cancer immunotherapy to monitor immune induction following immunotherapy, and to evaluate anti-tumor effects early after immunotherapy. We characterized status of immune cells, cytokines, chemokines and other immunosuppressive molecules in recurrent malignant glioma patients who received vaccinations of VEGF receptor peptides. Peripheral blood samples from patients who demonstrated positive radiologic response or stable disease revealed superior VEGFR-specific CTL reactivity and lower level of serum VEGF compared to samples from other patients with progressing malignant glioma. These data indicate that these parameters may be potential immune-biomarkers for evaluation of clinical activity of VEGFR-targeted vaccines.

Research Products

• [Journal Article] Pilocytic astrocytoma with anaplastic features presenting good long-term clinical course after surgery alone: a case report (2015)
  • Author(s): Saito K, Toda M, Yoshida K
  • Journal Title: Childs Nerv Syst Volume: 31 Issue: 1 Pages: 167-171
  • DOI: 10.1007/s00381-014-2509-1
  • Peer Reviewed / Open Access
• [Journal Article] Gruber's ligament as a useful landmark of Abducens nerve in transnasal approach (2015)
  • Author(s): Tomio R, Toda M, Sutiono AB, Horiguchi T, Aiso S, Yoshida K
  • Journal Title: J Neurosurg Volume: 122 Issue: 3 Pages: 499-503
  • DOI: 10.3171/2014.10.jns132437
  • Peer Reviewed / Open Access
• [Journal Article] Petrous Apex Cholesterol Granuloma: Importance of Pedicled Nasoseptal Flap in Addition to Silicone T-tube for Prevention of Occlusion of Drainage Route in Transsphenoidal Approach—A Technical Note (2015)
  • Author(s): Shibao S, Toda M, Tomita T, Saito K ,Kawase T, Ogawa K, Yoshida K
  • Journal Title: Neurologia medico-chirurgica Volume: 55 Issue: 4 Pages: 351-355
  • DOI: 10.2176/nmc.tn.2014-0254
  • NAID: 130005065370
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed / Open Access
• [Journal Article] Steroid Psychosis Caused by Perioperative Steroid Replacement for Pituitary Adenoma: A Case Report (2015)
  • Author(s): Mizutani K, Toda M, Kikuchi R, Uchida H, Yoshida K
  • Journal Title: The Keio Journal of Medicine Volume: 64 Issue: 1 Pages: 11-15
  • DOI: 10.2302/kjm.2014-0007-CR
  • NAID: 130005060926
  • ISSN: 0022-9717, 1880-1293
  • Peer Reviewed / Open Access
• [Journal Article] Various patterns of the middle cerebral vein and preservation of venous drainage during the anterior transpetrosal approach (2015)
  • Author(s): Shibao S, Toda M, Orii M, Fujiwara H, Yoshida K
  • Journal Title: J Neurosurg Volume: なし
  • Peer Reviewed
• [Journal Article] GH-producing Pituitary Adenoma and Concomitant Rathke’s Cleft Cyst: A case report and short review (2015)
  • Author(s): Tamura R, Takahashi S, Emoto K, Nagashima H, Toda M, Yoshida K
  • Journal Title: Case Reports in Neurological Medicine Volume: 2015 Pages: 948025-948025
  • DOI: 10.1155/2015/948025
  • Peer Reviewed / Open Access
• [Journal Article] Anterior petrosal approach (Letter to the Editor) (2014)
  • Author(s): Tomio R, Toda M, Yoshida K, Borghei-Razavi H
  • Journal Title: J Neurosurg Volume: 120 Issue: 5 Pages: 1249-1250
  • DOI: 10.3171/2013.10.jns132121
  • Peer Reviewed
• [Journal Article] Primary dural closure and anterior cranial base reconstruction using pericranial and nasoseptal multi-layered flaps in endoscopic-assisted skull base surgery (2014)
  • Author(s): Tomio R, Toda M, Tomita T, Yazawa M, Kono M, Ogawa K, Yoshida K
  • Journal Title: Acta Neurochirurgica Volume: なし Issue: 10 Pages: 1911-1915
  • DOI: 10.1007/s00701-014-2174-x
  • Peer Reviewed
• [Journal Article] Isolated Pituitary Tuberculoma (2014)
  • Author(s): Saito K, Toda M, Shido S, Tomita T, Ogawa K, Yoshida K
  • Journal Title: NMC Case Report Journal Volume: 1 Issue: 1 Pages: 33-36
  • DOI: 10.2176/nmccrj.2013-0330
  • NAID: 130004648821
  • ISSN: 2188-4226
  • Peer Reviewed
• [Journal Article] Analysis of the Bacterial Flora in the Nasal Cavity and the Sphenoid Sinus Mucosa in Patients Operated on with an Endoscopic Endonasal Transsphenoidal Approach (2014)
  • Author(s): Shibao S, Toda M, Tomita T, Ogawa K, Yoshida K
  • Journal Title: Neurologia medico-chirurgica Volume: 54 Issue: 12 Pages: 1009-1013
  • DOI: 10.2176/nmc.oa.2014-0129
  • NAID: 130004704537
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Journal Article] Transoral vs. Endoscopic Endonasal Approach for Clival/Upper Cervical Chordoma (2014)
  • Author(s): Shidoh S, Toda M, Kawase T, Nakajima H, Tomita T, Ogawa K, Yoshida K
  • Journal Title: Neurologia medico-chirurgica Volume: 54 Issue: 12 Pages: 991-998
  • DOI: 10.2176/nmc.st.2014-0135
  • NAID: 130004704542
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Journal Article] Functional analysis of a novel glioma antigen, EFTUD1 (2014)
  • Author(s): Saito K, Iizuka Y, Ohta S, Takahashi S, Nakamura K, Saya H, Yoshida K, Kawakami Y, Toda M
  • Journal Title: Neuro Oncol Volume: 16 Issue: 12 Pages: 1618-1629
  • DOI: 10.1093/neuonc/nou132
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunotherapy targeting cancer stem cells (2012)
  • Author(s): Kawakami Y, Matsushita M, Ueda R, Tsukamoto N, Ohta S.
  • Journal Title: Nihon Rinsho Volume: 70 (12) Pages: 2142-2146
  • NAID: 40019493388
  • Peer Reviewed
• [Presentation] ペプチドワクチンの臨床経験 (2015)
  • Author(s): 戸田正博
  • Organizer: 第10回信濃町脳腫瘍セミナー
  • Place of Presentation: 慶應義塾大学病院新教育研究棟講堂（東京都新宿区）
  • Year and Date: 2015-02-07
  • Invited
• [Presentation] 悪性神経膠腫に対するVEGFR1/2ワクチン療法 (2014)
  • Author(s): 柴尾俊輔、戸田正博、菊地亮吾、斉藤克也、植田 良、佐々木光、吉田一成
  • Organizer: 第32回日本脳腫瘍学会学術集会
  • Place of Presentation: シェラトン・グランデ・トーキョーベイ・ホテル（千葉県浦安市）
  • Year and Date: 2014-12-01
• [Presentation] 神経膠芽腫における新規標的抗原の発現・機能解析 (2014)
  • Author(s): 菊地亮吾、戸田正博、斉藤克也、吉田一成
  • Organizer: 日本脳神経外科学会第73回学術総会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2014-10-09
• [Presentation] 脳腫瘍の最新治療 (2014)
  • Author(s): 戸田正博
  • Organizer: 第19回日本脳腫瘍の外科学会 市民公開講座
  • Place of Presentation: 慶應義塾大学病院３号館北棟１階ラウンジ(東京都新宿区）
  • Year and Date: 2014-09-14
  • Invited
• [Presentation] Glioblastoma長期生存例の検討 (2014)
  • Author(s): 中川 佑、佐々木光、戸田正博、大平貴之、河瀬 斌、吉田一成
  • Organizer: 第19回日本脳腫瘍の外科学会
  • Place of Presentation: 東京ドームホテル(東京都文京区）
  • Year and Date: 2014-09-12
• [Presentation] 神経膠芽腫における新規標的抗原の発現解析 (2014)
  • Author(s): 菊地亮吾、戸田正博、斉藤克也、吉田一成
  • Organizer: 第32回日本脳腫瘍病理学会学術集会
  • Place of Presentation: あわぎんホール（徳島県郷土文化会館）（徳島県徳島市）
  • Year and Date: 2014-05-23
• [Book] 先端医療シリーズ45 臨床医のための最新脳神経外科 (2014)
  • Author(s): 戸田正博
  • Total Pages: 628
  • Publisher: 寺田国際事務所/先端医療技術研究所