HUMAN TNF-ALPHA

Description

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.

Originator

Genentech (US)

Uses

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)

Uses

TNF-α include stimulating growth of human fibroblasts and other cell lines activating polymorphonuclear neutrophils and osteoclasts and inducing interleukin-1, prostaglandin E2, and collagenase production.

brand name

Beromun

General Description

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.

Biochem/physiol Actions

Tumor Necrosis Factor-α (TNF-α) is a potent pro-inflammatory cytokine that plays a role in the rheumatoid arthritis pathology, psoriatic arthritis (PsA) and psoriasis. It stimulates interleukins IL-1 and IL-6. Polymorphism in the TNF-α gene is associated with destructive arthropathy in PsA. The post-translational modifications in TNF-a is crucial for its functionality.

Description

Tumor Necrosis Factor-a Human Recombinant produced in E.Coli is a single, non-glycosylated, polypeptide chain containing 158 amino acids (157 a.a. of the mature human TNF-alpha and an N-terminal methionine) and having a molecular mass of 17.5kDa.
The TNF-alpha is purified by standard chromatographic techniques.

Source

Escherichia Coli

Background

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, INS resistance, and cancer.