Lipid Nanoparticle-encapsulated mRNA-2752 Encoding Human OX40L, IL-23, and IL-36γ Plus Durvalumab Induces an Immunostimulatory Effect Within the Tumor Microenvironment in Patients with Advanced Solid
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- #mRNA therapeutic
- #tumor immunology
- #phase 1 clinical trial
- mRNA-2752 is an LNP-encapsulated mRNA therapy encoding OX40L, IL-23, and IL-36γ, showing immunomodulatory and antitumor effects in combination with CPIs in resistant models.
- In a phase 1 study with advanced solid tumor patients (134 total), MTD was not reached; recommended expansion dose was ≤8 mg. Safety was manageable, with grade 3 mRNA-2752-related AEs in 25.2% of Arm B patients.
- For CPI-resistant melanoma (n=28), confirmed ORR was 17.9% and disease control rate was 42.9%, indicating antitumor activity.
- Biomarker analyses revealed increased peripheral cytokine levels and sustained inflammatory responses in the TME, especially in responding patients.
- Findings support further investigation of mRNA-based therapeutics like mRNA-2752 plus durvalumab for advanced cancers, emphasizing its immunostimulatory profile.