Local administration of mRNA encoding cytokine cocktail confers potent anti-tumor immunity DOI Creative Commons
Zhigang Li, Ling Hu, Yiping Wang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 3, 2024

Immunotherapy using inflammatory cytokines, such as interleukin (IL)-2 and interferon (IFN)-α, has been clinically validated in treating various cancers. However, systemic immunocytokine-based therapies are limited by the short half-life of recombinant proteins severe dose-limiting toxicities. In this study, we exploited local immunotherapy intratumoral administration lipid nanoparticle (LNP)-encapsulated mRNA cocktail encoding cytokines IL-12, IL-7, IFN-α. The cytokine induced tumor regression multiple syngeneic mouse models anti-tumor immune memory one model. Additionally, checkpoint blockade further enhanced efficacy mRNAs. Furthermore, human mRNAs exhibited robust humanized models. Mechanistically, microenvironment inflammation, characterized T cell infiltration significant chemokine production.

Язык: Английский

Local administration of mRNA encoding cytokine cocktail confers potent anti-tumor immunity DOI Creative Commons
Zhigang Li, Ling Hu, Yiping Wang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 3, 2024

Immunotherapy using inflammatory cytokines, such as interleukin (IL)-2 and interferon (IFN)-α, has been clinically validated in treating various cancers. However, systemic immunocytokine-based therapies are limited by the short half-life of recombinant proteins severe dose-limiting toxicities. In this study, we exploited local immunotherapy intratumoral administration lipid nanoparticle (LNP)-encapsulated mRNA cocktail encoding cytokines IL-12, IL-7, IFN-α. The cytokine induced tumor regression multiple syngeneic mouse models anti-tumor immune memory one model. Additionally, checkpoint blockade further enhanced efficacy mRNAs. Furthermore, human mRNAs exhibited robust humanized models. Mechanistically, microenvironment inflammation, characterized T cell infiltration significant chemokine production.

Язык: Английский

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