Molecular Cancer: An in situ dendritic cell tumor vaccine based on engineered exosomes for breast cancer treatment

As the most potent antigen-presenting cells (APCs), dendritic cells (DCs) are central to initiating and regulating innate and adaptive immunity in the tumor microenvironment, with the ability to present tumor-associated antigens (TAAs) in the tumor microenvironment.
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As a result, a variety of experimental vaccines targeting DCs are available and in clinical trials to improve cancer immunotherapy

Targeted delivery of antigens and adjuvants to DCs in vivo is an important approach for developing DC vaccines
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The non-specific activation of systemic DCs and the preparation of optimal immunodominant tumor antigens are the main challenges currently facing

In recent years, exosomes, as a class of " natural nanoparticles " that can be used as drug delivery vehicles, have begun to receive widespread attention because of their low cytotoxicity, maximized drug bioavailability, and excellent target homing specificity.
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There are also a growing number of clinical trials exploring the therapeutic effects of exosomes

Recently, Wang Fubing , Yuan Chunhui and others from Zhongnan Hospital of Wuhan University published a research paper entitled: Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer in Molecular Cancer
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The research team constructed an engineered exosome combining a TLR3 agonist and an ICD inducer, HELA-Exos, which can in situ activate dendritic cells and specifically induce immune-derived cell death (ICD) in breast cancer cells
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It produces potent tumor suppression in mouse xenograft models of poorly immunogenic triple-negative breast cancer (TNBC) and in human patient-derived tumor organoids

Alpha-lactalbumin (α-LA), a mammary-specific immunodominant protein expressed in most human breast cancers, is further enriched on the surface of exosomes as a specific tumor-homing protein to enhance targeting ability and immunogenicity
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In this study, the research team developed and optimized a target-specific exosome loaded with Hiltonol (a TLR3 agonist, activating dendritic cells) and human neutrophil elastase (ELANE, an inducer of ICD).
Methods to construct in situ dendritic cell vaccines for breast cancer therapy
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In triple-negative breast cancer xenograft mouse models and patient tumor cell-derived triple-negative breast cancer organoids, this Hiltonol-ELANE-α-LA-engineered exosome (HELA-Exos), after systemic administration, has Powerful abilities that accumulate in cancer cells and produce better therapeutic effects
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Therefore, this combination of cell-free exosome-based TLR3 agonists and ICD inducers provides a powerful and novel development platform for designing dendritic cell vaccines for breast cancer therapy
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Collectively, HELA-Exos developed in this study improved subsequent tumor-reactive CD8+ T cell responses by promoting in situ type 1 conventional dendritic cell (cDC1) activation in triple-negative breast cancer xenograft mice Demonstrated robust antitumor activity in models and human triple-negative breast cancer organoids
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This strategy holds promise for generating in situ dendritic cell-generated tumor vaccines and can be extended to various types of cancer

Huang, L.