Yang et al. developed a novel nanoparticle cancer vaccine by incorporating the TLR7 agonist R837 (as an adjuvant to promote DC activation and maturation) into nanoparticles, coating the nanoparticles in tumor cell membrane (as a source of tumor-specific antigens), and modifying the particles with mannose (to enhance uptake by antigen-presenting cells). In vitro, the vaccine efficiently activated DCs, and in vivo, it induced antigen-specific cytolytic (CD107+) T cells, was prophylactically effective against B16-OVA melanoma tumors, and was therapeutically effective against established tumors, especially when combined with anti-PD-1.
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membrane modified by mannose. Poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles are firstly loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens. With further modification with mannose moiety (NP-R@M-M), the obtained nanovaccine shows enhanced uptake by antigen presenting cells such as dendritic cells (DCs), which would then be stimulated to the maturation status to trigger antitumor immune responses. With great efficacy to delay tumor development as a prevention vaccine, vaccination with such NP-R@M-M in combination with checkpoint-blockade therapy further demonstrates outstanding therapeutic efficacy to treat established tumors. Therefore, our work presents an innovative way to fabricate cancer nanovaccines, which in principle may be applied for a wide range of tumor types.
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Author Info: (1) (2) (3) (4) (5) (6) (7) (8)
