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Cytokines are a broad category of intercellular signaling proteins that are critical for intercellular communication in human health and disease. However, systematic profiling of cytokine signaling activities has remained challenging due to the short half-lives of cytokines, and the pleiotropic functions and redundancy of cytokine activities within specific cellular contexts.

Summary:

Lung metastases represent a major clinical challenge in advanced cancer, with poor survival rates and no effective therapies to prevent their development. Researchers at the National Cancer Institute (NCI) have developed C24:2, a first-in-class synthetic 3-O-sulfo-galactosylceramide analog. After lysosomal processing by dendritic cells, C24:2 switches immune specificity to activate type I NKT cells, triggering a potent IFN-γ–mediated Th1 response.

Pancreatic cancer is the fourth most common cause of cancer deaths in the U.S. The overall 5-year survival rate is 8.5%. Glypican-1 (GPC1) is a cell surface heparan sulfate proteoglycan protein overexpressed in pancreatic cancer. Due to preferential expression, GPC1 represents a potential candidate for targeted therapy for pancreatic cancer and other GPC1-expressing cancers, such as prostate.

The blood brain barrier (BBB) is a specialized endothelium that prevents the uptake of substances from the systemic circulation into the central nervous system. This barrier, while protecting the sensitive physiological environment of the brain, is also a major impediment in administering therapeutics that need to pass through the BBB. A drug delivery platform that could deliver therapeutic agents directly to the brain is needed, and could have wide ranging significance in a variety of psychiatric, oncology, infectious, and neurodegenerative diseases.

Computer and imaging technologies led to the development of digital pathology and the capture and storage of pathological specimens as digitally formatted images. The use of artificial intelligence (AI) in digital pathology, such as in three-dimensional (3D) reconstruction, requires analyses of high volumes of data. This resulted in increased demands for processing and acquisition of digital images of pathology samples. Increased usage cannot be met by the time-consuming, manual, and laborious methods currently used.

Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family, plays a critical role in regulating mitosis and cell cycle progression. Aberrant expression of Plk1 has been observed in a variety of human cancers, and it is known to be associated with tumorigenesis as well as poor prognosis in cancer patients. Unlike normal cells, some cancer cells are dependent on augmented Plk1 levels to remain viable and are killed when Plk1 function is attenuated.

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.  Thus, 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 promising new therapeutic approach is known as adoptive cell therapy.

Antiretroviral therapy (ART) has changed the prognosis of HIV-1 infection to a chronic illness that, in most cases, can be managed or controlled. Integrase strand transfer inhibitors (INSTIs) and reverse transcription inhibitors are essential components of ART drug cocktails. In compliant individuals, ART has been found to block viral replication completely. Additionally, blocking viral replication can prevent the emergence of drug resistance.

Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors such as camptothecin, rinotecan, and topotecan are widely used anti-cancer agents that work by stabilizing the TOP1-DNA cleavage complex.

One form of adoptive T cell therapy (ACT) consists of harvesting tumor infiltrating lymphocytes (TIL), screening and isolating TIL which display tumor antigen-specific T-cell receptors (TCR), expanding the isolated T cells in vitro, and reinfusing them into the patient for treatment. While highly active in the treatment of certain cancers (e.g., melanoma), current methods used to produce cancer-reactive T cells require significant time and may not adequately identify the desired TCRs which bind cancer targets.