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CO-sTiRNA + checkpoint inhibitors + CAR-Ts is a combination immunotherapy regimen being developed by Scopus BioPharma in collaboration with City of Hope. The core component, CO-sTiRNA (also known as CpG-STAT3siRNA), is a first-in-class targeted gene therapy that combines a STAT3-targeting small interfering RNA (siRNA) with a CpG oligonucleotide TLR9 agonist. This dual-action molecule is designed to silence the immunosuppressive STAT3 gene while simultaneously activating the innate immune system via TLR9. When used in combination with immune checkpoint inhibitors (such as PD-1/PD-L1 or CTLA-4 blockers) and chimeric antigen receptor T-cells (CAR-Ts), the regimen aims to overcome the immunosuppressive tumor microenvironment and enhance the persistence and efficacy of adoptive cell therapies. It is currently in preclinical development for B-cell non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and various solid tumors.
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