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Over 32 million Americans are living with Diabetes and newly diagnosed cases of type 1 and type 2 diabetes is increasing. A defining feature of type 2 diabetes mellitus (T2DM) is the accumulation of islet amyloid polypeptide (IAPP) fibrils in pancreatic islets. Such accumulations form amyloid plaques, referred to as islet amyloidosis. Mounting evidence suggests that islet amyloidosis plays a causative role in the development and progression of ß-cell dysfunction in T2DM.

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.

Despite several partially effective prophylactic vaccines for SARS-CoV-2 exist, patients worldwide still succumb to COVID-19. New therapeutics to treat this disease are still needed.  Upon host invasion, a critical step in the pathogenesis of COVID-19 is intracellular replication of SARS-CoV-2 before viral particles invade nearby healthy cells. This triggers an extreme inflammatory response that may lead to acute respiratory distress syndrome (ARDS) or transmission to another host.

Programed Death-Ligand 1 (PD-L1, also known as B7-H1 or CD274) is a cell surface protein that binds to Programmed Cell Death Protein 1 (PD-1, also known as CD279). An imbalance in PD-1/PD-L1 activity contributes to cancer immune escape.  PD-1 is expressed on the surface of antigen-stimulated T cells. The interaction between PD-L1 and PD-1 negatively regulates T cell-mediated immune responses. It has been suggested that disrupting the PD-L1/PD-1 signaling pathway can be used to treat cancers. The aberrant expression of PD-L1 on multiple tumor types supports this suggestion.

This technology describes additional methods of using the griffithsin anti-viral polypeptides described in related NCI invention (reference number E-106-2003).  Specifically, this invention describes the use of GRFT to inhibit viral infection of hepatitis C viral infection, a severe acute respiratory syndrome (SARS) viral infection, an H5N1 viral infection, or an Ebola viral infection. 

Three-dimensional (3D) cell cultures systems are important for studying cell biology because they provide in vivo-like microenvironments more physiologically relevant than two-dimensional (2D) culture systems. In 3D culture systems, cells are grown in culture matrixes and turn into spheroids and organoids later processed for downstream analysis by microscopy and histology techniques. The processing of 3D cultures for analysis by microscopy or histology is laborious and time-consuming due to incompatibility of the 3D culture vessels and the microscopy and pathology blocks.

Virus entry into a susceptible host cell is the first step in the formation of all viral diseases. Controlling viral infections by disrupting viral entry is advantageous for antibody-mediated neutralization by the host’s immune system and as a preventive and therapeutic antiviral strategy. Plant-derived carbohydrate-binding proteins (lectins) have emerged as a new class of antiviral biologics by taking advantage of a unique glycosylation pattern only found on the surface of viruses.

CD22 is a common cell surface glycoprotein expressed in B-cells and present in B-cell lymphomas; e.g., hairy cell leukemia (HCL), non-Hodgkins lymphoma (NHL), chronic lymphoblastic leukemia (CLL), and other cancers. It is therefore a target for cancer immunotherapy. Conjugation of anti-CD22 monoclonal antibodies with toxins or drugs has shown promise in clinical trials. However, all monoclonal anti-CD22 antibodies used in clinical trials are of murine origin.

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.

Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.