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.
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.
