Researchers at the National Cancer Institute (NCI) have developed a new method of improving the efficacy of vaccines in patients with human immunodeficiency virus (HIV) by activating Ras. This method can be used to develop more efficacious vaccine compositions by activating Ras before, during, or after vaccination. Additionally, the researchers discovered that modulation of the Ras pathways could be a predictive biomarker of protection against HIV.
Metastatic cancers cause up to 90% of cancer deaths, yet few treatment options exist for patients with metastatic disease. Adoptive transfer of T cells that express tumor-reactive T-cell receptors (TCRs) has been shown to mediate regression of metastatic cancers in some patients. Unfortunately, identification of antigens expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies. Thus, it is essential to find novel target antigens differentially expressed in cancer versus normal tissues.
Clinically known as Neuronal Ceroid-Lipofuscinoses (NCL), Batten disease, is a rare neuron killing disease and one of the lysosomal storage disorders (LSDs). It is associated with a mutation or lack of palmitoyl-protein thioesterase-1 (PPT1) gene. It manifests very early in a child's life causing absence of brain activity as early as 4 years of age.
This technology includes a vaccine for lowering plasma triglycerides by inducing the formation of autoantibodies against either ANGPTL3 or ANGPTL4, which are inhibitors of Lipoprotein Lipase. This was done by conjugating synthetic peptides based on ANGPTL3 or ANGPTL4 to virus- like particles (VLPS). Injection of the vaccine in animal models was shown to induce the autoantibody against the target and to lower plasma triglycerides.
This technology includes 1-13C-ketoglutarate which can be used for imaging the conversion to hydroxyglutarate (HG) or Gln in cancer cells with an IDH1 mutations by hyperpolarized MRI. The ability to detect the status of IDH1 mutations is clinically prognostic for multiple cancers. These exciting observations are limited by two factors, the major one being that the natural abundance of 13C at position C5 overlaps with 1-13C-2-hydroxyglutarate peak, which limits the sensitivity of analysis and prevents simultaneous observations of HG and Gln formation.
This technology includes structures and methods for cinching a band around the heart for treating conditions including tricuspid valve regurgitation (TR). When positioned appropriately along the atrioventricular groove, the band is tightened around the heart which narrows the tricuspid annulus and relieves TR.
This technology includes a new method to prepare very long chain fatty acids (VLCFA), which does not use the previously reported toxic mercury amalgam, for use as nutritional supplements, and as therapeutics for various diseases. The key coupling step involves an organocopper mediated coupling of the Grignard regent derived from the bromo alkyl tetraene with a bromoalkyl containing a protected alcohol. After the coupling the alcohol Is deprotected and oxidized to prepare the very long fatty acid. The synthetic approach is flexible and can be used to prepare the other VLCFA compounds.
This technology includes a peptide containing alternating Alanine and Lys(DOTA-Gd) residues can be used to increase the MRI relaxivity of a peptide. The low molecular weight construct can be appended to proteins, antibodies and peptides to increase MRI signals. This approach offers advantages over previous dendrimeric constructs.
This technology includes efficient lentiviral gene delivery system for both guide RNA and Cas9 endonuclease as a method to cure sickle cell disease. Gene correction is an ideal gene therapy strategy for hereditary disease, including sickle cell disease.
This technology includes the use of LZK and DLK inhibitors to be used for the treatment of head and neck squamous cell carcinoma (HNSCC) or lung squamous cell carcinoma (LSCC). Specifically, we demonstrate that inhibitors that can be repurposed to target LZK suppresses LZK kinase-dependent stabilization of MYC and activation of the PI3K/AKT pathway. In vivo preclinical cell line xenograft mouse model demonstrates that targeting LZK will suppress tumor growth. We also demonstrate that several additional compounds potently inhibit LZK and could serve as new therapeutic modalities.