Definition

A preparation of non-viral DNA plasmids encoding the human pro-inflammatory cytokine interleukin-12 (IL-12), constructed with a p21 promoter and devoid of an antibiotic resistance gene, with potential immunostimulating and antineoplastic activities. Upon administration of DNA plasmid encoding human IL-12 (hIL-12) phIL12 via intratumoral injection and electroporation, or gene electrotransfer (GET), the plasmid is introduced into human cells resulting in the expression and highly-localized secretion of IL-12 in the tumor microenvironment (TME). This activates the immune system by promoting the activation of natural killer cells (NKs), inducing the secretion of interferon-gamma (IFN-g) and promoting cytotoxic T-lymphocyte (CTL) responses against tumor cells. The switch from the constitutive promoter to the tumor-specific and genotoxic stress-inducible p21 promoter in the construction of phIL12 allows for high basal IL-12 expression in tumor cells. The lack of an antibiotic resistance gene improves the safety profile.