Synergistic effects of metal-organic nanoplatform and guanine quadruplex-based CpG oligodeoxynuceotides in therapeutic cancer vaccines with different tumor antigens

Xia Li; Mitsuhiro Ebara; Naoto Shirahata; Tomohiko Yamazaki; Nobutaka Hanagata

Article Synergistic effects of metal-organic nanoplatform and guanine quadruplex-based CpG oligodeoxynuceotides in therapeutic cancer vaccines with different tumor antigens

Xia Li (Research Center for Macromolecules and Biomaterials/Biomaterials Field/Smart Polymers Group, National Institute for Materials Science) ; Mitsuhiro Ebara (Research Center for Macromolecules and Biomaterials/Biomaterials Field/Smart Polymers Group, National Institute for Materials Science) ; Naoto Shirahata (Research Center for Materials Nanoarchitectonics (MANA)/Nanomaterials Field/Nanoparticle Group, National Institute for Materials Science) ; Tomohiko Yamazaki (Research Center for Macromolecules and Biomaterials/Biomaterials Field/Medical Soft Matter Group, National Institute for Materials Science) ; Nobutaka Hanagata (National Institute for Materials Science)

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Xia Li, Mitsuhiro Ebara, Naoto Shirahata, Tomohiko Yamazaki, Nobutaka Hanagata. Synergistic effects of metal-organic nanoplatform and guanine quadruplex-based CpG oligodeoxynuceotides in therapeutic cancer vaccines with different tumor antigens. Vaccines. 2024, 12 (6), 649.

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Oligodeoxynucleotides (ODNs) containing unmethylated cytosine-phosphate-guanosine (CpG) motifs are readily recognized by Toll-like receptor 9 on immune cells, trigger an immunomodulatory cascade, induce a Th1 -biased immune milieu and have a great potential as an adjuvant in cancer vaccines. In this study, a green one-step synthesis process was adopted to prepare amino-rich metal-organic nanoplatform (FN). The synthesized FN nanoplatform can simultaneously and ef-fectively load model tumor antigens (OVA) / autologous tumor antigens (dLLC) and im-munostimulatory CpG ODNs with an unmodified PD backbone and guanine-quadruplex structure to obtain various cancer vaccines. The FN nanoplatform and immunostimulatory CpG ODNs generate synergistic effects to enhance the immunogenicity of different antigens and inhibit the growth of established and distant tumors in both the murine E.G7-OVA lymphoma model and the murine Lewis lung carcinoma model. In E.G7-OVA lymphoma model, vaccination efficiently in-crease the CD4+, CD8+ and tetramer+CD8+ T cell populations in the spleens. In Lewis lung carci-noma model, vaccination efficiently increase the CD3+CD4+ and CD3+CD8+ T cell populations in the spleens and CD3+CD8+, CD3-CD8+ and CD11b+CD80+ cell populations in the tumors, suggesting the alteration of tumor microenvironment from cold to hot tumors.

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