ArticleMolecular therapy. Nucleic acids2023
Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists, and TGF-β antagonists.
Article in Molecular therapy. Nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models.Oncoimmunology · 2025Article
- Exploring the Potential and Advancements of Circular RNA Therapeutics.Exploration (Beijing, China) · 2025Review
- Therapeutic mRNA vaccine applications in oncology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Intraperitoneal administration of mRNA encoding interleukin-12 for immunotherapy in peritoneal carcinomatosis.Journal of nanobiotechnology · 2025Article
- Therapeutic Immunomodulation of Tumor-Lymphatic Crosstalk via Intratumoral Immunotherapy.Molecular pharmaceutics · 2024Review
- Better, Faster, Stronger: Accelerating mRNA-Based Immunotherapies With Nanocarriers.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumoral immunotherapy strategies for cancer based on interleukin-12 (IL-12)-encoding cDNA and mRNA are under clinical development in combination with anti-PD-(L)1 monoclonal antibodies. To make the most of these approaches, we have constructed chimeric mRNAs encoding single-chain IL-12 fused to single-chain fragment variable (scFv) antibodies that bind to transforming growth factor β (TGF-β) and CD137 (4-1BB). Several neutralizing TGF-β agents and CD137 agonists are also undergoing early-phase clinical trials. To attain TGF-β and CD137 binding by the constructions, we used bispecific tandem scFv antibodies (taFvs) derived from the specific 1D11 and 1D8 monoclonal antibodies (mAbs), respectively. Transfection of mRNAs encoding the chimeric constructs achieved functional expression of the proteins able to act on their targets. Upon mRNA intratumoral injections in the transplantable mouse cancer models CT26, MC38, and B16OVA, potent therapeutic effects were observed following repeated injections into the tumors. Efficacy was dependent on the number of CD8
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