Materials today. Bio · 2025
Biomimetic nanovesicle vaccines derived from dendritic cells sensitized with whole tumor antigens for melanoma immunotherapy.
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Lu Jiaye, Miao Fengze, Zhao Yingchao, Liu Jun, Meng Yu, Yan Han, Wang Ruyi, Zhu Quangang, Tai Zongguang, Chen Zhongjian
Аннотация
BACKGROUND: Cancer vaccine research has made significant progress in antigen discovery, delivery systems, and combination therapies. However, optimizing antigen selection and delivery remains a current challenge. To address this, we utilized oxidatively treated tumor cells as a source of antigens, effectively enhancing their immunogenicity. Inspired by the antigen delivery capabilities of dendritic cells (DCs) via extracellular vesicles, we developed a novel biomimetic nanovesicle vaccine, diA-MADCVac. This vaccine inherits the targeting ability of DCs, enabling precise antigen delivery to lymph nodes. Moreover, as a carrier, it efficiently delivers both adjuvants and intact tumor antigens, thereby playing a synergistic role in activating the immune system.
RESULT: By targeting lymph nodes, diA-MADCVac effectively induces DCs maturation, activating tumor-specific T cell responses and generating trained immune memory. Furthermore, in a melanoma mouse model, diA-MADCVac significantly altered the tumor microenvironment, triggering a strong anti-tumor immune response and inhibiting tumor growth. This effect was characterized by increased secretion of cytokines such as IFN-γ and TNF-α in the tumor, along with a higher number of infiltrating T cells, which enhanced the immune system's tumor-killing capacity.
CONCLUSION: This study introduces a novel vaccination strategy utilizing the DC-derived nanovesicle vaccine, diA-MADCVac. Systematic studies and experimental validation demonstrate that diA-MADCVac exhibits excellent biocompatibility, ensuring its safety for in vivo use. This nanovesicle serves as an effective carrier, efficiently delivering both adjuvants and antigens to lymph nodes, thereby enhancing DC-mediated anti-tumor immune responses. Additionally, diA-MADCVac promotes trained immunity and enhances the tumor-killing capacity of immune cells. With its unique advantages, diA-MADCVac offers an efficient, safe, and promising new approach for tumor treatment, providing renewed hope for cancer patients.
RESULT: By targeting lymph nodes, diA-MADCVac effectively induces DCs maturation, activating tumor-specific T cell responses and generating trained immune memory. Furthermore, in a melanoma mouse model, diA-MADCVac significantly altered the tumor microenvironment, triggering a strong anti-tumor immune response and inhibiting tumor growth. This effect was characterized by increased secretion of cytokines such as IFN-γ and TNF-α in the tumor, along with a higher number of infiltrating T cells, which enhanced the immune system's tumor-killing capacity.
CONCLUSION: This study introduces a novel vaccination strategy utilizing the DC-derived nanovesicle vaccine, diA-MADCVac. Systematic studies and experimental validation demonstrate that diA-MADCVac exhibits excellent biocompatibility, ensuring its safety for in vivo use. This nanovesicle serves as an effective carrier, efficiently delivering both adjuvants and antigens to lymph nodes, thereby enhancing DC-mediated anti-tumor immune responses. Additionally, diA-MADCVac promotes trained immunity and enhances the tumor-killing capacity of immune cells. With its unique advantages, diA-MADCVac offers an efficient, safe, and promising new approach for tumor treatment, providing renewed hope for cancer patients.