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INO-5412 + cadonilimab is a combination immunotherapy regimen being developed for the treatment of glioblastoma (GBM). INO-5412 is a DNA-based immunotherapy candidate that combines two distinct DNA plasmids: INO-5401, which encodes three tumor-associated antigens (hTERT, WT1, and PSMA) frequently overexpressed in GBM, and INO-9012, which encodes the pro-inflammatory cytokine interleukin-12 (IL-12) to enhance T-cell activation and infiltration. Cadonilimab (AK104) is a first-in-class bispecific antibody that simultaneously targets the programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) immune checkpoints. The combination strategy aims to prime a robust, antigen-specific T-lymphocyte response against the tumor while concurrently neutralizing multiple inhibitory pathways in the immunosuppressive GBM microenvironment. This regimen is currently being evaluated in the Phase 2 INSIGhT adaptive platform trial.
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