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.

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.

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).

Chimeric Antigen Receptors to CD276 for Treating Cancer

Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic.  Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR.  By engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction.  This is a promising new therapeutic approach known as adoptive cell therapy.