Biomimetic nanovesicle vaccines derived from dendritic cells sensitized with whole tumor antigens for melanoma immunotherapy.

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.