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| Home > Publications database > Durable clinical and immunologic response to an off-the-shelf EWSR1-FLI1 peptide vaccine in metastatic Ewing sarcoma. |
| Home > Publications database > Durable clinical and immunologic response to an off-the-shelf EWSR1-FLI1 peptide vaccine in metastatic Ewing sarcoma. |
| Journal Article | DKFZ-2026-01970 |
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2026
Springer Nature
[London]
Abstract: Ewing sarcoma is a rare, fusion-driven malignancy with poor prognosis in the metastatic setting, for which no established immunotherapeutic treatment is currently available. Fusion breakpoints are rational precision immunotherapy targets, yet clinical evidence of immunogenicity is scarce. We administered an off-the-shelf multi-peptide vaccine spanning the type 1 EWSR1-FLI1 breakpoint to a patient with high-burden metastatic Ewing sarcoma following multimodal therapy. Vaccinations were combined with GM-CSF and topical imiquimod. Longitudinal immune monitoring by in vitro peptide stimulation and intracellular cytokine staining revealed de novo polyfunctional CD4⁺ T-cell responses against all four fusion-derived peptides, first detectable by month 7 and persisting beyond two years. Treatment was well tolerated with only grade 1 local reactions. Durable disease stability was maintained for more than 26 months. These first-in-human data support the feasibility, safety, and immunogenicity of a fusion-derived peptide vaccine and warrant further evaluation of precision immunotherapy in sarcomas driven by recurrent gene fusions.
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