A Preclinical Orthotopic Model for Glioblastoma Multiforme that Represents Key Pathways Aberrant in Human Brain Cancer

Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Scientists at the National Cancer Institute (NCI) have developed and characterized an orthotopic genetically engineered mouse (GEM)-derived model of GBM that closely recapitulates various human GBM subtypes and is useful for preclinical evaluation of candidate therapeutics.

First in class Small Molecule Agonists of the mammalian Relaxin family receptor 1 (RXFP1) and use in treatment of cancer, fibrotic, and vascular disorders (HHS Ref No. E-145-2024-0-US-02)

It is well documented in literature that activation of RXFP1 by relaxin induces: 1) up-regulation of the endothelin system which leads to vasodilation; 2) extracellular matrix remodeling through regulation of collagen deposition, cell invasiveness, proliferation, and overall tissue homeostasis; 3) a moderation of inflammation by reducing levels of inflammatory cytokines, such as TNF-a and TGF-b; and 4) angiogenesis by activating transcription of VEGF.

Methods of Detecting Loss of Heterozygosity and Damaging Mutations in Immune-Related Genes Using Liquid Biopsies

Summary: 
The National Cancer Institute (NCI) seeks co-development partners and/or licensees for a liquid biopsy diagnostic assay capable of detecting loss of heterozygosity (LOH) and somatic mutations in genes important for antigen processing and presentation and interferon-γ response pathways.

Method for HLA LOH Detection in Liquid Biopsies

Human leukocyte antigen (HLA) LOH (LOH) is a known resistance mechanism by which cancers evade T cell receptor-(TCR-)based immunotherapies. This class of therapies includes immune checkpoint inhibition (ICI, e.g., Pembrolizumab), engineered TCR (T cell receptor)-T cell adoptive transfer, tumor infiltrating lymphocytes (TIL), T-cell engagers, and other modalities. Dozens of therapies in this category were developed with many in clinical trials. The resistance mechanism noted here, HLA LOH, causes these therapies to fail.

Intralipid as a Contrast Agent to Enhance Subsurface Blood Flow Imaging

This technology includes a blood flow imaging method that allows for a higher density of smaller particles to be detected. Current imaging methods that are based on Doppler measurements are limited by the discontinuity in the capillary flow in the space between red blood cells. The core technology is to use a scattering agent to enhance capillary flow or microcirculation. This technology has been tested for optical coherence Doppler tomography, but can be expended to any Doppler based flow imaging techniques such as laser speckle imaging.

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.

Angubindin-1 Peptide for Transient Blood-Brain Barrier Opening to Boost Chemotherapy in Malignant Glioma

This technology includes a first-in-class synthetic peptide, angubindin-1, designed to temporarily relax the blood-brain barrier (BBB)—the tightly sealed network of brain blood vessel cells that normally blocks most drugs—from the inside. By binding the tricellular tight-junction protein angulin-1/LSR, the peptide creates a reversible “molecular doorway” that lets cancer medicines such as liposomal doxorubicin (Doxil®) reach tumors in the central nervous system (CNS).