PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy

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2021
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Nature Communications. Nature Publishing Group. 2021, 12(1), 2935. eISSN 2041-1723. Available under: doi: 10.1038/s41467-021-23244-3
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With emerging supremacy, cancer immunotherapy has evolved as a promising therapeutic modality compared to conventional antitumor therapies. Cancer immunotherapy composed of biodegradable poly(lactic-co-glycolic acid) (PLGA) particles containing antigens and toll-like receptor ligands induces vigorous antitumor immune responses in vivo. Here, we demonstrate the supreme adjuvant effect of the recently developed and pharmaceutically defined double-stranded (ds)RNA adjuvant Riboxxim especially when incorporated into PLGA particles. Encapsulation of Riboxxim together with antigens potently activates murine and human dendritic cells, and elevated tumor-specific CD8+ T cell responses are superior to those obtained using classical dsRNA analogues. This PLGA particle vaccine affords primary tumor growth retardation, prevention of metastases, and prolonged survival in preclinical tumor models. Its advantageous therapeutic potency was further enhanced by immune checkpoint blockade that resulted in reinvigoration of cytotoxic T lymphocyte responses and tumor ablation. Thus, combining immune checkpoint blockade with immunotherapy based on Riboxxim-bearing PLGA particles strongly increases its efficacy.

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ISO 690KÖRNER, Julia, Dennis HORVATH, Valerie L. HERRMANN, Anna MACKERRACHER, Bruno GANDER, Hideo YAGITA, Jacques ROHAYEM, Marcus GRÖTTRUP, 2021. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy. In: Nature Communications. Nature Publishing Group. 2021, 12(1), 2935. eISSN 2041-1723. Available under: doi: 10.1038/s41467-021-23244-3
BibTex
@article{Korner2021PLGAp-53746,
  year={2021},
  doi={10.1038/s41467-021-23244-3},
  title={PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy},
  number={1},
  volume={12},
  journal={Nature Communications},
  author={Körner, Julia and Horvath, Dennis and Herrmann, Valerie L. and MacKerracher, Anna and Gander, Bruno and Yagita, Hideo and Rohayem, Jacques and Gröttrup, Marcus},
  note={Article Number: 2935}
}
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