Abstract
Personalized vaccines demonstrate remarkable potential in leveraging tumor-specific adaptive immunity for cancer therapy. Nevertheless, current platforms face persistent challenges, including premature systemic clearance and imprecise antigen-presenting cell targeting, culminating in transient and inefficient antitumor immunity. Furthermore, the technical complexity, extended timelines, and prohibitive costs required for tumor-specific neoantigen identification continue to impede the clinical translation of personalized cancer vaccines. Here, we report a tumor-derived extracellular vesicle-based scaffold vaccine that elicits robust and durable antitumor immunity for personalized cancer immunotherapy. Following subcutaneous administration, the in situ-formed hydrogel vaccine serves as a sustained reservoir for tumor-derived extracellular vesicle antigens and adjuvants while recruiting antigen-presenting dendritic cells to accumulate within the scaffold. Upon exposure to this antigen-rich depot, immature dendritic cells undergo efficient activation, with subsequently matured dendritic cells migrating to draining lymph nodes, where they induce potent and persistent tumor-specific CD8+ T-cell responses that suppress tumor progression across multiple murine models. Specifically, when using tumor-derived extracellular vesicles isolated from surgically excised tumor tissues, the patient-tailored vaccines demonstrate remarkable efficacy in preventing postoperative recurrence. Our findings validate the robust and durable therapeutic efficacy of this vaccine platform, highlighting its potential as a customizable strategy for personalized cancer immunotherapy.
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Data availability
The RNA sequencing data have been deposited in the NCBI Sequence Read Archive (SRA) under accession number PRJNA1330898. All other data supporting the findings of this study are included in the main article, supplementary information, or source data file. Source data are provided with this paper.
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Acknowledgements
This study was supported by National Natural Science Foundation of China (82473851 to F.W., 82373358 and 82472142 to L.D., 82227801 to W.X., 82573527 to J.P.); National Key Research and Development Program of China (2025ZD01903300 and 2022YFC3501905 to F.W.); Major Natural Science Research Projects of Shanghai Municipal Education Commission (2023ZKZD23 to W.X.); Scientific Research Specialization on Post-market Clinical Research of Innovative Drugs of National Healthcare Commission (WKZX2023CX100002 to J.P.); Shanghai Top Priority Research Center Project (2023ZZ02014 to W.X.); Shanghai High-level Local Universities Construction Program; Shanghai Rising-Star Program (23QA1405900 to L.D.); National Outstanding Young Physician of China (2022YQ014 to L.D.); Shanghai Rising-Star Young Medical Talents Program (to L.D.); Physician-Scientist Development Award from Shanghai Immune Therapy Institute (to L.D.); Shanghai Jiao Tong University 2030 Program (to L.D.).
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J.P., F.W., L.D., and W.X. supervised the study; Q.C., C.J., F.W., and L.D. designed the experiments; X.D. constructed prostate orthotopic model and breast cancer metastasis model; M.T., Q.S., C.H., and Z.P. assisted in animal experiments; Q.C. completed analysis of transcriptome sequencing data; Q.C., F.W., L.D., and J.P. analyzed data and organized figures; J.P., W.X., L.D., and F.W. provided funding; Q.C., F.W., and J.P. wrote the manuscript. All authors revised the manuscript.
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Chen, Q., Jiang, C., Du, X. et al. Spatiotemporally engineered tumor-derived extracellular vesicle-based scaffold vaccine for personalized cancer immunotherapy. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70924-z
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DOI: https://doi.org/10.1038/s41467-026-70924-z
