Tasonermin (Beromun)

概览

Tasonermin is a tumor necrosis factor alpha used along with surgery to remove soft tissue sarcomas of the limbs.

作用机制

Since tasonermin is recombinant TNF-α, it functions exactly as endogenous TNF-α does. The direct cytotoxic effect of TNF-α is mediated by TNF-α receptor 1 . The bound receptor activates the well-reviewed death receptor pathway involving the activation of initiator caspases 8 and 9 then ultimately ending in the activation of effector caspase 3 which begins the process of apoptosis. The effect on tumor vasculature is mediated by the inflammatory signalling pathway of TNF-α, the NFκB pathway . This pathway is also activated by TNFR1 when bound to TNFα. The NFκB transcription factor increases expression of proteins in vascular endothelial cells. These proteins include cell adhesion molecules, inflammatory mediators like prostaglandins and interleukins, and growth factors . TNF-&alpha also increases the expression of inducible nitric oxide synthase via this pathway which contributes to the generation of reactive nitrogen species . These species are able to damage cells in the tumor and microvasculature. The cytokines produced from NFκB activation and TNF-&aplha; itself serve to activate the cells of the immune system which further damage tumor cells with respiratory bursts, phagocytosis and subsequent breakdown of the cell, and release of cytotoxic enzymes. The antigen presenting cells which phagocytose the tumor cells are able to activate lymphocytes and allow the adaptive immune system to further damage the tumor tissue .

适应症

For use in adults as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in palliative care, for irresectable soft tissue sarcoma of the limbs . Used in combination with melphalan via mild hyperthermic isolated limb perfusion.

• Irresectable soft tissue sarcoma of the limb