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

Julia Koerner, Dennis Horvath, Valerie L. Herrmann, Anna MacKerracher, Bruno Gander, Hideo Yagita, Jacques Rohayem and Marcus Groettrup ()
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Julia Koerner: Division of Immunology, Department of Biology, University of Konstanz
Dennis Horvath: Division of Immunology, Department of Biology, University of Konstanz
Valerie L. Herrmann: Division of Immunology, Department of Biology, University of Konstanz
Anna MacKerracher: Division of Immunology, Department of Biology, University of Konstanz
Bruno Gander: Institute of Pharmaceutical Sciences, ETH Zürich
Hideo Yagita: Juntendo University School of Medicine
Jacques Rohayem: Riboxx GmbH, BioInnovationszentrum
Marcus Groettrup: Division of Immunology, Department of Biology, University of Konstanz

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-23244-3

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