Sunday, January 23, 2022

Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models

Other uses of mRNA than SARS-CoV-2/Covid-19 vaccines! Cancer is history!

"Cytokine-based treatments for cancer have been hindered by both off-target toxicity and difficulty in achieving local delivery. To address these challenges, Hotz et al. developed a saline-formulated mixture of four mRNAs delivered by intratumoral injection. The mRNAs encoded interleukin-12 (IL-12) single chain, interferon-α, granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. The combination led to robust antitumor immune responses and tumor regression in multiple mouse models, including models with more than one tumor. Together, these data support further development of cytokine-encoding mRNAs as a treatment for cancer."

From the abstract:
"Local immunotherapy ideally stimulates immune responses against tumors while avoiding toxicities associated with systemic administration. Current strategies for tumor-targeted, gene-based delivery, however, are limited by adverse effects such as off-targeting or antivector immunity. We investigated the intratumoral administration of saline-formulated messenger (m)RNA encoding four cytokines that were identified as mediators of tumor regression across different tumor models: interleukin-12 (IL-12) single chain, interferon-α (IFN-α), granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. Effective antitumor activity of these cytokines relied on multiple immune cell populations and was accompanied by intratumoral IFN-γ induction, systemic antigen-specific T cell expansion, increased granzyme B+ T cell infiltration, and formation of immune memory. Antitumor activity extended beyond the treated lesions and inhibited growth of distant tumors and disseminated tumors. Combining the mRNAs with immunomodulatory antibodies enhanced antitumor responses in both injected and uninjected tumors, thus improving survival and tumor regression. Consequently, clinical testing of this cytokine-encoding mRNA mixture is now underway."

Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models (no public access)

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