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The tumor microenvironment (TME) is a complex mixture of cell types whose interactions affect tumor growth and clinical outcome. Recent studies using fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (RNAseq) to elucidate tissue composition and cell-cell interactions in the TME led to improved biomarkers of patient response and new treatment opportunities. However, the use of FACS is limited to simultaneously measuring the expression of a few protein markers, whereas the use of single-cell RNAseq has been limited due to cost and scarcity of fresh tumor biopsies.

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.

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.

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. 

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.

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.

Synovial sarcoma is a cancer affecting mesenchymal cells in connective tissues. This rare cancer is typically linked to genetic abnormalities or exposure to radiation. Metastatic growth throughout the body can occur primarily through blood circulation. More than 90% of synovial sarcomas show a characteristic t(X;18)(p11;q11) translocation involving the SYT and SSX genes. The resulting SYT-SSX abnormal fusion protein causes misregulation of downstream gene expression, leading to tumor formation.

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.