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Cellular Immunotherapy for Pathological Retinal Neovascularization

Research Project

Project/Area Number 17591851
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKEIO UNIVERSITY

Principal Investigator

ISHIDA Susumu  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (10245558)

Co-Investigator(Kenkyū-buntansha) KAWAKAMI Yutaka  Keio University, School of Medicine, Professor, 医学部, 教授 (50161287)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsangiogenesis / immunity / VEGF / retina / AMD / 加齢黄斑変性
Research Abstract

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly people over the age of 50 in the developed countries. AMD is complicated by choroidal neovascularization (CNV), during which the choroidal new vessels invade the subretinal space through Bruch's membrane to form the fibrovascular proliferative tissue containing vascular endothelial cells, fibroblasts, retinal pigment epithelial (RPE) cells and various inflammatory cells. Our recent reports demonstrated CD8+ cytotoxic T cell (CTL)-mediated suppression of physiologic and pathologic retinal new vessels. In tumor models, specific immunization targeting VEGFR2, which are highly expressed in endothelial cells, was reported to inhibit tumor growth and angiogenesis. Accordingly, we hypothesized a possible immunological therapy for CNV by inducing CTL responses targeting VEGFR2, which is a specific molecule highly expressed in CNV-associated endothelial cells. Thus, we examined whether experimental CNV is suppressed by inducing specific cellular immunity against VEGFR2 via vaccination with dendritic cells (DCs), professional antigen-presenting cells.
In the paper already submitted, we showed, for the first time to our knowledge, that the induction of peptide-specific cellular immunity targeting endothelial cells inhibits CNV generation. Vaccination of DCs pulsed with the epitope peptide VEGFR2400-408 elicited the CTL responses specific for the peptide. Additionally, CD8 T cells were shown as the major effectors in the immunological treatment. These data indicate the new concept of CTL-mediated specific immunotherapy for CNV.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (15 results)

All 2007 2006 Other

All Journal Article (15 results)

  • [Journal Article] Role of nonproteolytically activated prorenin in pathologic, but not physiologic, retinal neovascularization.2007

    • Author(s)
      Satofuka S, Ishida S, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 48

      Pages: 422-429

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of nonproteolytically activated prorenin in pathologic, but not physiologic, retinal neovascularization.2007

    • Author(s)
      Satofuka S, Ishida S et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. 48

      Pages: 422-429

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin.2006

    • Author(s)
      Satofuka S, Ishida S, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. 47 47

      Pages: 2686-2692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization.2006

    • Author(s)
      Nagai N, Ishida S, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 26

      Pages: 2252-2259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin.2006

    • Author(s)
      Satofuka S, Ishida S, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. 47

      Pages: 2686-2692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroprotective effects of angiotensin II type 1 receptor (AT1R) blocker, telmisartan via modulating AT1R and AT2R signaling in retinal inflammation.2006

    • Author(s)
      Kurihara T, Ozawa Y, Shinoda K, Nagai N, Inoue M, Oike Y, Tsubota K, Ishida S, Okano H.
    • Journal Title

      Invest Ophthalmol Vis Sci 47

      Pages: 5545-5552

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Angiotensin II type 1 receptor-mediated inflammaton is required for choroidal neovascularization.2006

    • Author(s)
      Nagai N, Oike Y, Izumi-Nagai K, Urano T, Kubota Y, Noda K, Ozawa Y, Inoue M, Tsubota K, Suda T, Ishida S.
    • Journal Title

      Arteriosclear Thromb Vasc Biol 26

      Pages: 2252-2259

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin.2006

    • Author(s)
      Satofuka S, Ichihara A, Nagai N, Yamashiro K, Koto T, Shinoda H, Noda K, Ozawa Y, Inoue M, Tsubota K, Suzuki F, Oike Y, Ishida S.
    • Journal Title

      Invest Ophthalmol Vis Sci 47

      Pages: 2686-2892

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Visual sensations during pars plana vitrectomy under retrobulbar anesthesia.2006

    • Author(s)
      Sugisaka E, Shinoda K, Ishida S, Imamura Y, Ozawa Y, Nakajima T, Shinoda H, Suzuki K, Kawaguchi N, Inoue M et al.
    • Journal Title

      Ophthalmology 113

      Pages: 1886-1886

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Detecting vitreomacular adhesions in eyes with asteroid hyalosis with triamcinolone acetonide.2006

    • Author(s)
      Yamaguchi T, Inoue M, Ishida S, Shinoda K.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol 244

      Pages: 1-4

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 糖尿病網膜症- 手術に踏み切るタイミング2006

    • Author(s)
      石田 晋
    • Journal Title

      臨床眼科 60

      Pages: 126-130

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of choroidal neovascularization by inhibiting angiotensin-converting enzyme : Minimal role of bradykinin.

    • Author(s)
      Nagai N, Ishida S, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interleukin-6 receptor-mediated activation of STAT3 promotes choroidal neovascularization.

    • Author(s)
      Izumi-Nagai K, Ishida S, et al.
    • Journal Title

      Am J Pathol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Suppression of choroidal neovascularization by inhibiting angiotensin-converting enzyme : Minimal role of bradykinin.

    • Author(s)
      Nagai N, Ishida S et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interleukin-6 receptor-mediated activation of STAT3 promotes choroidal neovascularization.

    • Author(s)
      Izumi-Nagai K, Ishida S, et al.
    • Journal Title

      Am J Pathol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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