Although vaccination is historically one of the most successful strategies for the prevention of infectious diseases, development of vaccines for cancer and many chronic infections, such as HIV, ...malaria, and tuberculosis, has remained a challenge. Strong and long-lasting antigen-specific T cell responses are critical for therapy of these diseases. A major challenge in achieving a robust CD8+ T cell response is the requirement of spatio-temporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we discuss the development of nanoparticle vaccine (nanovaccine) that modulates the innate immune system and enhances adaptive immunity with reduced toxicity. We address how nanovaccines can integrate multiple functions, such as lymph node targeting, antigen presentation, and stimulation of innate immunity, to achieve a robust T cell response for immunotherapy.
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Solid cancers are able to escape immune surveillance and are resistant to current treatment in immunotherapy. Recent evidence indicates the critical role of the stimulator of interferon genes (STING) ...pathway in antitumor immunity. STING-targeted activation is extensively investigated as a new strategy for cancer therapy. Previously, we reported a safe and efficacious STING-activating nanovaccine to boost systemic tumor-specific T cell responses in multiple tumor models. Local radiotherapy has been reported to not only reduce tumor burden but also enhance local antitumor immunity in a STING-dependent manner. In this study, we demonstrate that combination of these two modalities leads to a synergistic response with long-term regression of large established tumors in two mouse tumor models. The percentage of CD8+ T cells increased significantly in primary tumors after combination therapy. Mechanistically, the augmented T cell responses of radiotherapy and nanovaccine is STING pathway dependent. Furthermore, nanovaccine synergizes with radiotherapy to achieve a better therapeutic effect in distal tumors. These findings suggest that combination of local radiotherapy with systemic PC7A nanovaccine offers a useful strategy to improve the therapeutic outcome of late stage solid cancers.
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