PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy
| Autor: | Dennis Horvath, Valerie Laura Herrmann, Hideo Yagita, Anna MacKerracher, Julia Koerner, Marcus Groettrup, Bruno Gander, Jacques Rohayem |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
THP-1 Cells medicine.medical_treatment General Physics and Astronomy Translational immunology Ligands chemistry.chemical_compound 0302 clinical medicine Cancer immunotherapy Polylactic Acid-Polyglycolic Acid Copolymer Cytotoxic T cell Receptors Immunologic Immune Checkpoint Inhibitors Cells Cultured Cancer Mice Inbred BALB C Multidisciplinary Chemistry Drug Synergism PLGA medicine.anatomical_structure Treatment Outcome 030220 oncology & carcinogenesis DEAD Box Protein 58 Tumour immunology Female Immunotherapy Adjuvant T cell Science Mice Transgenic macromolecular substances Cancer Vaccines General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Immune system ddc:570 Cell Line Tumor medicine Animals Humans technology industry and agriculture General Chemistry Neoplasms Experimental Immune checkpoint Toll-Like Receptor 3 Mice Inbred C57BL 030104 developmental biology Cancer research Microscopy Electron Scanning Nanoparticles |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) Nature Communications, 12 (1) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-23244-3 |
| Popis: | 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. + Nature Communications, 12 (1) ISSN:2041-1723 |
| Databáze: | OpenAIRE |
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