Novel TRAIL-upregulating miRNA for Treating Cancer

Fox Chase Cancer Center Background
Clinical development of TRAIL/Apo2L based therapies has been of great interest in cancer. This is because TRAIL/Apo2L ligand has unique ability to induce cell death in cancer cells while sparing normal and untransformed cells. This selective antitumor potential of the TRAIL pathway has been harnessed by development of different therapeutic approaches including recombinant (rh)TRAIL and TRAIL-receptor agonist antibodies such as mapatumumab and lexatumumab. Many TRAIL-based therapies have proven successful in preclinical studies and safe in early phase clinical trials. However, clinical trial results suggest several limitations of rhTRAIL and TRAIL receptor agonists such as serum half-life, hepatotoxicity, stability, tumor-specific cytotoxicity and biodistribution being the most evident. Hence, there is still an unmet clinical need for TRAIL-based anti-tumor agents with increased efficacy and safety.
Technology Overview
Renowned scientists at the Fox Chase Cancer Center have identified a TRAIL-inducing miRNA with anti-proliferative and pro-apoptotic effects in a broad panel of cancer types. The researchers have demonstrated that miRNA-induced TRAIL upregulation is causal of Type I Interferon signaling; which can be activated by an innate immunity response to specific types of miRNAs. The current invention demonstrates the therapeutic use and anti-cancer effects of the first-in class described miRNA with TRAIL-inducing ability via immune mechanisms. The described invention is also the first to demonstrate the use of miRNA mimics for both targeting their endogenous targets and activating an immune response, selective to kill cancer cells. The researchers are also in process of describing additional miRNAs with similar TRAIL-inducing capabilities and characterizing this unique class of miRNAs. The described invention offers an alternative to treating mutant p53 harboring tumors, which comprise ~ 60-70% solid tumors.

Novel target-based and cancer-selective therapeutic for treating colorectal, ovarian, breast, lung cancers or melanoma
Novel modulator of anti-tumor immune response
Prospected synergistic effect with pharmaceutical agents that upregulate TRAIL or activate TRAIL signaling pathway


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