High expression of CD47, a cell surface receptor on several types of cancer cells, has been identified as a ‘don’t eat me signal’ that inhibits their killing by macrophages or NK cells. Conversely, the CD47 antibody B6H12 that blocks SIRPα binding enhances macrophage-dependent clearance of tumors in several mouse models, although others have shown that such clearance can be independent of SIRPα signaling.
This technology includes mechanobiological nucleic acid nanoassemblies-based platforms with dynamically controlled efficiency of T-cell activation. T-cells are the central players in adaptive immune response led by a T-cell receptor (TCR) centric machinery. Current T-cell activation strategy (e.g., micron-scale beads) focuses on 2D TCR-agonist biomimetic surfaces and biomimetic 2D immune synapses with planar traction, which requires non-physiological hyper-stimulatory cytokines levels (e.g., IL-2), and thus, is incompatible with clinical applications.
This technology from the NCI Molecular Imaging Program relates to a Zirconium-89 (89Zr)-oxine complex for cell labeling, tracking of labeled cells by whole-body positron emission tomography/computed tomography (PET/CT) imaging, and associated methods. A long half-life of 89Zr (78.4 hours), high sensitivity of PET, and absence of background signal in the recipient enable tracking cells over a week using low levels of labeling radioactivity without causing cellular toxicity.
Proviral Integration for the Moloney murine leukemia virus (PIM) kinases are overexpressed in many solid cancers – including prostate, breast, colon, endometrial, gastric and pancreatic. High of PIM1 expression is predictive of poor survival in multiple cancer types. While several selective pan-PIM inhibitors were developed and tested in clinical trials, all ultimately increased PIM1-3 protein levels and developed intrinsic resistance.