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    Home > Biochemistry News > Biotechnology News > New anti-cancer mRNA therapy: more than 80% of mouse tumors have completely disappeared, and the efficacy of PD-1 antibody is improved

    New anti-cancer mRNA therapy: more than 80% of mouse tumors have completely disappeared, and the efficacy of PD-1 antibody is improved

    • Last Update: 2021-10-11
    • Source: Internet
    • Author: User
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    Article source: Medical Rubik's Cube Pro

    Author: Li Yuan

    mRNA therapy was first used in tumor treatment, by injecting mRNA encoding cytokines and other specific proteins into the tumor to activate the immune response
    .


    However, this technology also faces the problems of off-target toxicity and difficulty in intratumoral administration.


    Sanofi cooperated with BioNTech to develop a melanoma mRNA therapy.
    In the cover paper of Science Translational Medicine on September 8, researchers introduced the preclinical development data of this therapy
    .

    The above picture shows the distribution of CD8 T cells (green), CD4 T cells (red) and regulatory T cells (yellow) in mouse tumors after intratumoral treatment with mRNA encoding cytokines.
    The nuclei are shown in blue ( Source: Science Translational Medicine)

    This therapy consists of 4 types of IL-12 single-chain, type I interferon alpha (IFN-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-15 sushi (IL-15 receptor).
    The sushi domain of the α chain is fused to IL-15) mRNA mixture
    .


    Repeated injection of this mRNA mixture into the tumor can effectively control the growth of the tumor, and the tumors of most tumor-bearing mice have completely resolved (8 out of 10 B16F10 and 9 out of 10 CT26)


    Source: Science Translational Medicine

    Moreover, the treatment was well tolerated, and no animal weight loss was observed during the study, and the long-term survival rate of the animals was also improved
    .

    After the administration of the intratumoral mRNA mixture, the researchers performed immunofluorescence microscopy on the B16F10 tumor and observed that the mRNA mixture changed the tumor microenvironment, CD4+ and CD8+ T cell infiltration increased, and in a variety of tumor models, intratumoral injection of mRNA The mixture can induce effective effector T cell responses and protective immune memory against multiple antigens
    .

    Source: Science Translational Medicine

    The anti-tumor activity of this mRNA mixture can also extend to distant tumor locations and control the growth of lung tumor metastases
    .

    Source: Science Translational Medicine

    In addition, the combination of mRNA mixture and PD-1 inhibitor can further enhance its anti-tumor effect
    .


    In the three tumor models tested, the combined use of cytokine mRNA and PD-1 antibody increased the overall survival of mice


    Source: Science Translational Medicine

    The clinical trial of this cytokine mRNA mixture has started (NCT03871348) and is currently in phase I clinical trials


    Reference materials:

    Hotz C, Wagenaar TR, Gieseke F.


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