HUMAN TNF-ALPHA

Tasonermin was launched in Germany for the treatment of soft tissue sarcoma of the limbs. Recent literature is scarce for this compound. It is the first tumor necrosis factor (TNF) launched for cancer treatment to date and works through destruction of tumor blood vessels. This recombinant protein is expressed in E. coil and purified. Tasonermin is too toxic for systemic use and consequently is being used in isolated limb perfusion (ILP) for sarcoma and malignant melanoma. The product has shown notable efficacy when used in combination with melphalan to prevent amputation. In four European clinical trials involving 260 patients destined for amputation or mutilating surgery, Beromun enabled durable limb salvage in 80% of the patients. Due to the complexity of ILP, the application of tasonermin is restricted to clinical centers with sufficient experience and facilities including radionucleide-based continuous monitoring of leakage from the isolated circuit during ILP and postoperative intensive care surveillance.

Tumor Necrosis Factor-a human has been used:

• as a permeability inducing agent for endothelial cell monolayer permeability assay
• as a reactive oxygen species inducer in primary rat cardiac microvascular endothelial cells (RCMVECs)
• in the activation of nuclear factor kappa B (NF-κB) in human embryonic kidney cells (HEK293), neuroblastoma SH-SY5Y cells and HeLa cells
• in the stimulation of the human keratinocyte cell line(HaCaT) and human coronary artery endothelial cells (HCAECs)

The TNFα (tumor necrosis factor α) gene is mapped to human chromosome 6p21.33. TNFα is a member of TNF superfamily. TNF-α has a palmitoyl group in the cysteine residue and is phosphorylated in the transmembrane region serine residue.