4.8 Article

Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies

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JOURNAL OF CONTROLLED RELEASE
卷 353, 期 -, 页码 423-433

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ELSEVIER
DOI: 10.1016/j.jconrel.2022.11.053

关键词

Dendritic cell derived exosomes; Neoantigen; Personalized nanovaccine; Cancer immunotherapy

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This study developed a nanovaccine platform utilizing dendritic cell derived exosomes carriers and patient-specific neoantigens for individualized cancer immunotherapies. The nanovaccine demonstrated efficient cargo loading and transportation to lymph nodes, inducing potent antigen specific immune responses with high safety. Importantly, it effectively inhibited tumor growth, prolonged survival, and eliminated lung metastasis in melanoma models. Additionally, the exosome-based nanovaccine showed superior antitumor response compared to liposomal formulation due to the presence of exosomal proteins. These findings present a promising strategy for cell free vaccines and personalized nanotechnology in cancer immunotherapy.
Despite the promising potential of cancer vaccine, their efficacy has been limited in clinical trials and improved methods are urgently needed. Here we designed a nanovaccine platform that contains dendritic cell derived exosomes carriers and patient-specific neoantigens for individualized immunotherapies. The nanovaccine exhibited convenient cargo loading and prolonged cargo transportation to the lymph nodes, followed by eliciting potent antigen specific broad-spectrum T-cell and B-cell-mediated immune responses with great biosafety and biocompatibility. Strikingly, delivery of neoantigen-exosome nanovaccine significantly prohibited tumor growth, prolonged survival, delayed tumor occurrences with long-term memory, eliminated the lung metastasis in the therapeutic, prophylactic and metastatic B16F10 melanoma as well as therapeutic MC-38 models, respectively. Additionally, exosome-based nanovaccine demonstrated synergistic antitumor response superior to liposomal formulation due to presence of exosomal proteins. Collectively, our research indicated improved strategies for cell free vaccines and suggested exosome-based nanoplatform for cancer immunotherapy and personalized nanotechnology. These findings represent a powerful pathway to generate individualized nanovaccine rapidly for clinical application.

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