A New Molecular Scaffold for Targeting hRpn13 as a Treatment for Cancer

This technology includes a new chemical scaffold (with lead compound XL5) against hRpn13 that induces apoptosis, which may have clinical efficacy against cancer. The structure of XL5-conjugated hRpn13 guided the design of XL5-PROTAC degrader compounds that exhibit greater efficacy than previous hRpn13-targeting compounds, as evaluated by selectivity for hRpn13, induction of apoptosis, and loss of cell viability. In cells, XL5-PROTACs revealed the presence of a truncated hRpn13 product that binds to proteasomes and is selectively degraded by XL5-PROTACs.

Genetic Manipulation of Natural Killer Cells to Express c-MPL Growth Factor Receptor as a Therapy for Cancer

This technology includes genetic manipulation of natural killer (NK) cells to express thrombopoietin receptor (c-MPL) growth factor receptor as strategy to augment NK cell proliferation and anti-tumor immunity. Many investigational adoptive immunotherapy regimens utilizing NK cells require the administration of IL-2 or IL-15 cytokines to support the survival and function of the cells in patients, however administration of these cytokines causes a number of serious dose-dependent toxicities.

Evans Blue Modified Small Molecule-based Prostate-specific Membrane Antigen (PSMA) Radiotherapy and Nuclear Imaging

This technology includes anti-PSMA antibody labeled with 177Lu, which has shown to be an effective treatment for prostate cancer. Several small molecules targeting PSMA were also evaluated in prostate cancer patients labeled with betta emitters such as 177Lu. The most common one is 177Lu-PSMA-617 which is under clinical evaluation in many countries. Usual treatment in patients in most clinical trials was composed of up to 3 cycles of 177Lu-PSMA-617.

Concurrent Use of Atorvastatin During Chemotherapy Reduces Cisplatin-induced Ototoxicity

This technology includes the use of atorvastatin, a medication to manage hypercholesterolemia, as a method to protect patients receiving cisplatin from hearing loss. Cisplatin chemotherapy is indicated in various cancer types in adults and children and is known to cause hearing loss. A patient on atorvastatin during chemotherapy is 46% less likely to acquire a significant cisplatin-induced hearing loss relative to a non-statin user. Atorvastatin is an FDA-approved medication routinely prescribed and well-tolerated clinically.

Functions and Targets of Therapeutic MicroRNAs to Treat and Diagnose Cancer

This technology includes a method to identify potentially therapeutic microRNAs in cancer, particularly squamous cell carcinoma of the head and neck (HNSCC). This approach first utilizes a large and publicly available expression dataset, which is then validated by a smaller independent dataset to determine deregulated microRNAs expression. These results are then intersected with in vitro functional anti-proliferative screening data to select for microRNAs that play a functional tumor suppressive role and likely serve as therapeutic targets.

P2Y14 Receptor Antagonists for the Treatment of Inflammatory Diseases, Including Pulmonary and Renal Conditions and Chronic Pain

This technology includes the development of selective P2Y14R antagonists for the treatment of asthma, sterile inflammation of the kidney, diabetes, and neurodegeneration. The P2Y14 receptor (P2Y14R) is a target for the treatment of inflammatory diseases, including pulmonary and renal conditions. Selective P2Y14R antagonists have demonstrated efficacy in animal models of asthma, pain, diabetes, and acute kidney injury. However, the prototypical antagonist is not optimal for in vivo administration, as it displays a low oral bioavailability.

Selective A3 Adenosine Receptor Agonists for the Treatment of Chronic Neuropathic Pain and Other Conditions

This technology includes the creation and use of A3 adenosine receptor (A3AR)-selective agonists for treating chemotherapy-induced peripheral neuropathy, chronic neuropathic pain, rheumatoid arthritis, psoriasis, and other conditions. A3 receptors for adenosine are found in most cells and endogenous activation of the A3 receptors can result in apoptosis, thereby relieving the inflammation or targeting a tumor. A3AR agonists have been a promising strategy for the treatment of various diseases.

Modulating Autophagy as a Treatment for Lysosomal Storage Diseases

Researchers at NIAMS have developed a technology for treatment of lysosomal storage diseases by inhibition of autophagy. Pompe disease is an example of a genetic lysosomal storage disease caused by a reduction or absence of acid alpha-glucosidase (GAA). Patients with Pompe disease have a lysosomal buildup of glycogen in cardiac and skeletal muscle cells and severe cardiomyopathy and skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme replacement therapy is quite ineffective for the skeletal muscle myopathy.

Engineered Human Induced Pluripotent Stell Cell (iPSC) Lines for Multiple Therapeutic and Diagnostic Uses

This technology includes ten engineered human induced pluripotent stem cell (iPSC) lines with reported genes inserted into safe harbor sites for use in therapy and diagnostic screening assay development as well as basic stem cell biology research. These cell lines have the potential to differentiate into all cells in the body, and theoretically can proliferate/self-renew indefinitely.