Accordingly, there are agonistic antibodies in preclinical and clinical development against several TNF receptor family members, such as TNF-related apoptosis inducing ligand (TRAIL) receptor 1, TRAIL receptor 2, glucocorticoid-induced tumor necrosis factor receptor (GITR), CD137 and CD40.
The second type of TRAIL receptors act as decoy receptors and these are TRAIL R3 (decoy decoy receptor 1), TRAIL R4 (decoy decoy receptor 2) and osteoprotegerin (OPG) [ 10].
Of these, only TRAIL receptor 1 (TRAIL-R1, DR4) and TRAIL receptor 2 (TRAIL-R2, DR5) mediate apoptosis as they contain a functional death domain (DD) required for apoptosis signaling.
CD95 (Fas/APO-1), TNFR1, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2 comprise the best characterized DRs [ 2, 22, 23].
Formation of the pro-apoptotic death-inducing signaling complex (DISC) can be initiated in cancer cells via binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to its two pro-apoptotic receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2.
Mapatumumab is a fully human monoclonal antibody that is agonistic to the TRAIL Receptor 1 (TRAIL-R1).
To this end, alternative pathways, such as the one activated by death receptors including Fas/Apo-1, or tumour necrosis factor-related apoptosis-inducing ligand Receptor 1 (TRAIL-R1) and TRAIL Receptor 2 (TRAIL-R2), are being explored for cancer treatment.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) binds to its receptors, TRAIL-receptor 1 (TRAIL-R1) and TRAIL-receptor 2 (TRAIL-R2), leading to apoptosis by activation of caspase-8 and the downstream executioner caspases, caspase-3 and caspase-7 (caspase-3/7).
These cell lines expressed death receptors TRAIL-receptor 1 (TRAIL-R1) and TRAIL-R2, which were unaltered by treatment with CDDP, as assessed by flow cytometry.
TRAIL binding to TRAIL receptor 1 (TRAIL-R1) or TRAIL-R2 induces formation of a chain-like death-inducing signaling complex (DISC).
TRAIL mediates apoptosis through two death receptors, TRAIL-receptor 1 (TRAIL-R1, DR4, TNFRSF10A) and TRAIL-receptor 2 (TRAIL-R2, DR5, TNFRSF10B).
