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Immunotherapy is a cutting-edge new category of treatment that aims to harness and, in some cases, modify the patient’s own immune cells to improve their ability to cure diseases. It can be an effective approach for a variety of conditions, ranging from cancer to inflammatory diseases.  However, a number of obstacles to the overall success of immunotherapy still exist.  For example, reactivity against a target antigen can be attenuated or the lifespan of the “modified” immune cells can be too short.

There are no effective treatments for Alzheimer’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk.

There is no known cure for Alzheimer’s disease, a brain disorder that severely affects memory, thinking, learning, and organizing skills. It eventually decreases a person’s ability to carry out simple, daily activities. It is predicted that over 14 million Americans will develop Alzheimer’s without effective treatment options. Mild cognitive impairment (MCI) is a stage prior to Alzheimer’s when memory problems become noticeable. A patient’s ability to function and live independently remain intact as the brain compensates for disease-related changes.

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.

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.

Mutation of amino acid 61of the neuroblastoma rat sarcoma viral oncogene homologue (NRAS) is a known driver of oncogenesis in melanoma. Glutamine (Q) to lysine (K) mutation at this position of NRAS is prevalent in approximately 10% of all melanoma cases and associated with aggressive tumors and low patient survival. Therefore, Q61K mutated NRAS is an important candidate for targeted therapies, including cellular immunotherapy. 

Bioluminescence imaging with luciferin-luciferase pairs is a well-established technique for tracking cells and other biological features in animal models. Bioluminescent is a chemical process which does not require an external input for excitation. Bioluminescent imaging is often limited to monitoring single processes in vivo due to the lack of distinguishable probes. Additionally, existing probes typically operate with light in the visible range, which is highly scattered and exhibits poor tissue penetration. 

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.

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. 

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.