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Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular

Han Zhang1, Koh-Hei Sonoda, Kuniaki Hijioka

  • 1Department of Ophthalmology, Kyushu University, Higashi-Ku, Fukuoka, Japan.

Biochemical and Biophysical Research Communications
|April 3, 2009
PubMed

Insights

New immunotherapy targeting Flk-1 shows promise for treating ocular neovascularization (NV), a leading cause of blindness. This approach, using DNA vaccines and T cell therapy, suppressed pathological blood vessel growth in preclinical models.

Area of Science:

  • Ophthalmology
  • Immunology
  • Vascular Biology

Background:

  • Ocular neovascularization (NV) is a major cause of vision loss.
  • Current therapies for ocular NV are limited due to poorly understood pathogenesis.
  • Flk-1 is overexpressed on proliferating endothelial cells in ocular NV.

Purpose of the Study:

  • To investigate the potential of antiangiogenic immunotherapy targeting Flk-1 for ocular NV.
  • To evaluate the efficacy of a DNA vaccine and adoptive T cell therapy.

Main Methods:

  • Developed an oral DNA vaccine encoding Flk-1 using attenuated Salmonella typhimurium.
  • Administered the DNA vaccine to induce anti-Flk-1 CD8+ T cells.
  • Evaluated the vaccine's effect on laser-induced choroidal NV.
  • Assessed the impact of adoptive T cell transfer on oxygen-induced preretinal NV and physiological revascularization.

Main Results:

  • The oral DNA vaccine significantly suppressed the development of choroidal NV.
  • Adoptive transfer of vaccine-induced CD8+ T cells reduced pathological preretinal NV.
  • This immunotherapy facilitated physiological revascularization without affecting normal neonatal retinal vascular development.

Conclusions:

  • Antiangiogenic immunotherapy targeting Flk-1, including vaccination and adoptive T cell therapy, shows therapeutic potential for ocular NV.
  • This strategy may offer a novel treatment avenue for blinding ocular diseases characterized by NV.

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