Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity CD16 and CCR7

A highly efficient method to genetically modify natural killer (NK) cells to induce expression of high affinity CD16 (HA-CD16) through mRNA electroporation, to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated by CD16+ NK cells following adoptive NK cell transfer, but most humans express CD16 which has a relatively low affinity for IgG1 antibodies.

Potent Nucleotide Inhibitors of Ecto-5'-Nucleotidase (CD73)

These small molecules are novel nucleotide derivatives, containing either a purine or pyrimidine nucleobase, that competitively block the enzyme CD73, also known as ecto-5'-nucleotidase. This enzyme converts extracellular AMP (not a potent activator of adenosine receptors) to adenosine (the native activator of 4 subtypes of adenosine receptors. CD73 inhibitors are being used, in clinical trials and preclinical research, in conjunction with cancer immunotherapy.

A Novel Demodulation System in X-ray Imaging

In various x-ray imaging methods, including scattering correction and phase contrast imaging, intensity modulation in space is introduced into the projection images by the use of masks, gratings, or apertures. The present invention relates to a process to demodulate the modulation. The current demodulation processes are either to remove the modulation pattern through digital processing or to move the modulation pattern on the detector in a series of images that requires mechanical movements of a component and tends to lose some information of the imaged object.

A Novel X-ray Grating to Enhance Phase Contrast Imaging

The present invention relates to improving x-ray phase contrast imaging. The invention discloses a novel grating interferometer for phase contrast imaging with hard x-rays that overcomes limitations in the level of sensitivity by utilizing the advantages of far-field interferometers. The novel design and fabrication process can easily acquire absolute and differential phase images of lightly absorbing samples.

Miniature Serial Microtome for Block-Face Imaging

A microtome device is used in a variety of microcopy techniques to remove very thin (e.g., in the tens of nanometers range) portions from the top of a sample between successive images. This technology discloses a design for a microtome device that offers several unique features and advantages over commercially available microtomes. A prototype of the microtome has been built and demonstrated to work with a serial block-face scanning electron microscopy in order to serially collect ultrathin sections from plastic embedded biological tissues, specifically from brain tissues.

A Current Amplifier for Local Coil Pre-amplification of NMR/MRI Signals

The magnetic resonance imaging (MRI) systems are used for a variety of imaging application. The present invention discloses an improving MRI device and method by amplifying signals received by resonant NMR coils of MRI systems. It utilizes positive feedback from low-noise Field-Effect Transistor to amplify the signal current that can be coupled out to receiving loops positioned externally without loss in sensitivity. Therefore, the NMR coil can be flexibly positioned near internal tissues and used to develop high-resolution images in highly invasive situations.

Potentiating Antibody Therapy by Targeting Complement Deposited on Cancer Cells

Monoclonal antibodies (mAbs) have become a mainstay of therapy for many cancers. However, antibody therapy is not completely effective in some applications due to loss of the target surface antigen on cancer cells. Such mAb-induced “escape variants” are no longer sensitive to the therapeutic mAb therapy. It was observed that the escape variants carried covalently bound complement activation fragments, especially C3d. NIH inventors have generated several C3d-specific mouse and rabbit monoclonal antibodies to re-target cells that have escaped from mAb therapy.

Highly Potent and Selective Deubiquitinating Enzyme Inhibitor

Available for licensing are inhibitors that target the USP1/ UAF1 deubiquitinating enzyme (DUB) complex. The FDA approval and commercial success of Velcade®, a small molecule proteasome inhibitor, has established the ubiquitin-proteasome system (UPS) as a valid target for anticancer treatment. However, proteasome inhibitors in general suffer from a narrow therapeutic index and acquired resistance. A promising alternative to proteasome inhibition has been to target the enzymes upstream of proteasome-mediated protein degradation, i.e.