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Publication : RNA aggregates harness the danger response for potent cancer immunotherapy.

First Author  Mendez-Gomez HR Year  2024
Journal  Cell Volume  187
Issue  10 Pages  2521-2535.e21
PubMed ID  38697107 Mgi Jnum  J:348551
Mgi Id  MGI:7639526 Doi  10.1016/j.cell.2024.04.003
Citation  Mendez-Gomez HR, et al. (2024) RNA aggregates harness the danger response for potent cancer immunotherapy. Cell 187(10):2521-2535.e21
abstractText  Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.
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