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sPD1-TruncT1 DNA vaccine is an experimental cancer vaccine consisting of a DNA plasmid that encodes a soluble form of Programmed Cell Death Protein 1 (sPD1) fused to a truncated version of the TWIST1 transcription factor. TWIST1 is a basic helix-loop-helix transcription factor overexpressed in various solid tumors, including melanoma, breast, and colon cancer, where it contributes to tumorigenesis, metastasis, and epithelial-mesenchymal transition. The vaccine is designed to be delivered via in vivo electroporation. The sPD1 component acts as a molecular adjuvant to enhance T cell recruitment and activation, potentially by blocking the PD-1/PD-L1 inhibitory pathway or acting as a decoy. The truncated TWIST1 (TruncT1) focuses the immune response on immunodominant T cell epitopes found in the C-terminal conserved region of the protein, aiming to improve efficacy and reduce potential off-target toxicity compared to full-length TWIST1 vaccines. Preclinical studies in murine models have demonstrated that this construct elicits robust and polyfunctional TWIST1-specific T cell responses, showing efficacy in both preventive and therapeutic settings.
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