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Pigbak#2-PE38 is a **recombinant immunotoxin** designed as a fusion protein that combines the single-chain Fab antibody Pigbak#2, which binds in a TNF-α (tumor necrosis factor alpha)-dependent manner, with the cytotoxic PE38 domain derived from *Pseudomonas exotoxin A*. This fusion protein was engineered to be secreted by genetically modified *Escherichia coli* BL21(DE3) Δlpp, a "leaky" strain optimized for extracellular secretion. Pigbak#2-PE38 exhibits potent, selective, TNF-α-dependent cytotoxicity toward cancer cells, notably showing strong anti-tumor activity in murine melanoma models. The mechanism leverages the presence of TNF-α in the tumor microenvironment to enable cell-specific targeting and internalization, followed by delivery of the PE38 toxin that induces cell death via inhibition of protein synthesis. Delivery via intratumorally injected bacteria leads to accumulation in tumors, upregulation of TNF-α, and significant immunomodulatory and anti-tumor effects[1][2].
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