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pIL-12(P2A) is a bicistronic DNA plasmid expression vector designed to encode the two subunits of Interleukin-12 (IL-12), p35 and p40, separated by a picornavirus-derived 2A (P2A) self-cleaving peptide sequence. Developed by OncoSec Medical, this construct is intended for intratumoral delivery followed by electroporation (IT-EP). The inclusion of the P2A linker allows for the co-translational cleavage of the polyprotein into individual subunits, ensuring stoichiometric expression and efficient assembly of the functional IL-12p70 heterodimer. This localized production of IL-12, a potent pro-inflammatory cytokine, aims to stimulate the tumor microenvironment by activating natural killer (NK) cells and cytotoxic T lymphocytes, thereby inducing both local and systemic (abscopal) anti-tumor immune responses. Preclinical data indicates that the P2A-linked construct provides superior protein expression and anti-tumor efficacy compared to earlier internal ribosome entry site (IRES) or fusion protein-based designs. It has been investigated for the treatment of solid tumors, including melanoma and Merkel cell carcinoma.
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