Chimeric Fas-TNFR1 death receptor (Fas-TNFR1)

The Chimeric Fas-TNFR1 death receptor is an engineered protein designed to modulate cell death pathways for therapeutic purposes, particularly in the treatment of solid tumors. It is most prominently known as the functional component of the gene therapy ofranergene obadenovec (VB-111), where it consists of the extracellular and transmembrane domains of the human tumor necrosis factor receptor 1 (TNFR1) fused to the intracellular signaling domain of the Fas (CD95) receptor [39, 42, 45]. This chimeric structure functions as a "signal converter," enabling the induction of Fas-mediated apoptosis in response to the binding of tumor necrosis factor-alpha (TNF-α), a cytokine typically elevated in the tumor microenvironment [41, 45, 47]. By placing the expression of this receptor under the control of an endothelium-specific promoter, the therapy selectively targets and destroys angiogenic tumor blood vessels, leading to vascular disruption and tumor starvation [40, 41, 43]. Additionally, similar chimeric constructs are being explored in CAR-T cell research as "switch receptors" to protect immune cells from inhibitory signals or to enhance their activation by converting death signals into survival ones [1, 26]. Clinical development of therapies utilizing this receptor has focused on aggressive malignancies such as glioblastoma and platinum-resistant ovarian cancer [44, 47, 48].

Other names

Fas-TNFR1 switch receptorFas-TNFR1 fusion proteinTNFR1-Fas chimeraOfranergene obadenovec transgene productFas-c

Induction of apoptosis via signal conversion and vascular disruption