mRNA expression triple immunoregulatory factor Moderna immunotherapy shows preliminary anti-cancer activity

A few days ago, Moderna announced the preliminary phase 1 clinical trial results of its mRNA immunotherapy mRNA-2752 for the treatment of solid tumors and lymphoma patients

mRNA-2752 is composed of mRNAs encoding three immunoregulatory factors, which are expressed separately: OX40 ligand, which can enhance the expansion and survival of CD4 and CD8 positive T cells; IL-23, which is a promoter of the IL-12 family Inflammatory cytokines can activate dendritic cells and other immune cells; IL-36γ, which is a pro-inflammatory cytokine of the IL-1 family, can help the maturation of dendritic cells

▲The mechanism of action of mRNA-2752 (picture source: Moderna official website, click to see a larger image)

The latest published clinical trial results showed that in patients receiving local injection of mRNA-2752 and durvalumab systemic therapy, all doses of the combination therapy showed good tolerability, and the recommended dose for the extended trial part is currently increased to 8mg mRNA-2752+ durvalumab

Long-lasting partial remission was observed in a patient with squamous cell bladder cancer with low PD-L1 levels and a patient with diffuse large B-cell lymphoma whose disease progressed after CAR-T cell therapy

Signs of immune regulation were found in the tumor microenvironment of the lesions receiving local injection treatment and the tumor microenvironment of the non-injected lesions, including increased T cell expansion, PD-L1 levels, and increased transcription characteristics of inflammatory T cells and dendritic cells.

Reference materials:

[1] Moderna Announces Presentation of Interim Data from Phase 1 Study of mRNA Triplet Program at 2021 SITC Annual Meeting.

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