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Background <p>Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss. Although anti-VEGF therapy is effective, frequent injections carry risks and may not fully address the underlying disease process. Wilms’ tumor gene 1 (WT1), an upstream regulator of VEGF, is expressed in choroidal neovascular membranes and may represent a biologically relevant adjunctive target in nAMD. This pilot study evaluated the safety, tolerability, and immunogenicity of WT1-targeted dendritic cell (WT1-DC) vaccines and their effects on retinal morphology and visual function in nAMD patients, with secondary endpoints including clinical outcomes and in vitro WT1-specific T-cell responses.</p> Methods <p>Two patients initially received three monthly intravitreal injections of aflibercept (2&#xa0;mg each), followed by 15 subcutaneous vaccinations with WT1-DCs. The vaccine contained both WT1-specific helper and killer peptides restricted to HLA-A*24:02. In addition, a helper peptide restricted to MHC class II and class I (HLA-A*02:01/02:06) was used.</p> Results <p>WT1-DC vaccination was well tolerated, and adverse events were limited. One patient maintained a stable retinal morphology and visual acuity without additional anti-VEGF therapy, whereas the other experienced recurrent subretinal fluid accumulation requiring intermittent rescue injections and a gradual decline in best-corrected visual acuity. Peripheral blood mononuclear cells from both patients exhibited functional CD4 + and CD8 + T-cell responses during vaccination and produced IFN-γ and TNF-α upon WT1 peptide stimulation in vitro.</p> Conclusions <p>WT1-DC vaccination was feasible and well tolerated in these two patients who were clinically managed within the nAMD spectrum. Exploratory laboratory findings suggested WT1 peptide–responsive T-cell activity in vitro, but clinically meaningful in vivo immunogenicity was not established. Given the extremely small sample size, the confounding effect of prior anti-VEGF loading therapy, and diagnostic uncertainty regarding CNV etiology in one patient, no conclusions regarding therapeutic efficacy can be drawn. These observations support further investigations of WT1-DC vaccination in larger controlled studies.</p> Trial registration <p>Japan Registry of Clinical Trials (jRCTc030210068), registered May 7, 2021.</p>

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WT1-pulsed dendritic cell vaccination for neovascular age-related macular degeneration: a phase I pilot feasibility study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月23日

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  • Masaki Nakamura,
  • Shigeo Koido,
  • Tuuse Bito,
  • Hiroshi Horiguchi,
  • Yoko Shimizu,
  • Masamori Shimabuku,
  • Junichi Taguchi,
  • Hisato Gunji,
  • Haruo Sugiyama,
  • Tadashi Nakano

摘要

Background

Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss. Although anti-VEGF therapy is effective, frequent injections carry risks and may not fully address the underlying disease process. Wilms’ tumor gene 1 (WT1), an upstream regulator of VEGF, is expressed in choroidal neovascular membranes and may represent a biologically relevant adjunctive target in nAMD. This pilot study evaluated the safety, tolerability, and immunogenicity of WT1-targeted dendritic cell (WT1-DC) vaccines and their effects on retinal morphology and visual function in nAMD patients, with secondary endpoints including clinical outcomes and in vitro WT1-specific T-cell responses.

Methods

Two patients initially received three monthly intravitreal injections of aflibercept (2 mg each), followed by 15 subcutaneous vaccinations with WT1-DCs. The vaccine contained both WT1-specific helper and killer peptides restricted to HLA-A*24:02. In addition, a helper peptide restricted to MHC class II and class I (HLA-A*02:01/02:06) was used.

Results

WT1-DC vaccination was well tolerated, and adverse events were limited. One patient maintained a stable retinal morphology and visual acuity without additional anti-VEGF therapy, whereas the other experienced recurrent subretinal fluid accumulation requiring intermittent rescue injections and a gradual decline in best-corrected visual acuity. Peripheral blood mononuclear cells from both patients exhibited functional CD4 + and CD8 + T-cell responses during vaccination and produced IFN-γ and TNF-α upon WT1 peptide stimulation in vitro.

Conclusions

WT1-DC vaccination was feasible and well tolerated in these two patients who were clinically managed within the nAMD spectrum. Exploratory laboratory findings suggested WT1 peptide–responsive T-cell activity in vitro, but clinically meaningful in vivo immunogenicity was not established. Given the extremely small sample size, the confounding effect of prior anti-VEGF loading therapy, and diagnostic uncertainty regarding CNV etiology in one patient, no conclusions regarding therapeutic efficacy can be drawn. These observations support further investigations of WT1-DC vaccination in larger controlled studies.

Trial registration

Japan Registry of Clinical Trials (jRCTc030210068), registered May 7, 2021.