Tumor vaccines trigger
tumor-specific immune responses to prevent or treat
tumors by activating the hosts' immune systems, and therefore, these
vaccines have potential clinical applications. However, the low immunogenicity of the
tumor antigen itself and the low efficiency of the
vaccine delivery system hinder the efficacy of
tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects. Here, we constructed a
nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10
cancer cell membranes and the unmethylated
cytosine-
phosphate-
guanine (CpG) adjuvant. Hyperbranched PEI25k was used to load unmethylated
cytosine-
phosphate-
guanine (CpG) through electrostatic adsorption to prepare PEI25k/CpG nanoparticles (PEI25k/CpG-NPs). CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology, followed by the cell surface translocation of
calreticulin (CRT) to induce immunogenic cell death (ICD) in vitro. Finally, the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered
cancer cell membrane-coated nanoparticles (DBE@CCNPs). DBE@CCNPs could promote endocytosis of
antigens and adjuvants in murine bone marrow derived dendritic cells (BMDCs) and induce their maturation and
antigen cross-presentation. To avoid
immune checkpoint molecule-induced T cell dysfunction, the
immune checkpoint inhibitor, the anti-PD-L1 antibody, was introduced to boost
tumor immunotherapy through a combination with the DBE@CCNPs
nanovaccine. This combination
therapy strategy can significantly alleviate
tumor growth and may open up a potential strategy for clinical
tumor immunotherapy.