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Human immunodeficiency virus (HIV) remains a major global health challenge despite the advancement made in development of effective antiretrovirals (ARVs). ARVs are effective at limiting replication and spread of the virus, and progression to acquired immuno-deficiency syndrome (AIDS). However, ARVs often lead to emergence of drug-resistant virus strains insensitive to treatment and with toxic effects following long-term usage.

Researchers at the National Cancer Institute (NCI) have developed a new method of improving the efficacy of vaccines in patients with human immunodeficiency virus (HIV) by activating Ras. This method can be used to develop more efficacious vaccine compositions by activating Ras before, during, or after vaccination. Additionally, the researchers discovered that modulation of the Ras pathways could be a predictive biomarker of protection against HIV.

Metastatic cancers cause up to 90% of cancer deaths, yet few treatment options exist for patients with metastatic disease. Adoptive transfer of T cells that express tumor-reactive T-cell receptors (TCRs) has been shown to mediate regression of metastatic cancers in some patients. Unfortunately, identification of antigens expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies. Thus, it is essential to find novel target antigens differentially expressed in cancer versus normal tissues.

This technology includes the use of LZK and DLK inhibitors to be used for the treatment of head and neck squamous cell carcinoma (HNSCC) or lung squamous cell carcinoma (LSCC). Specifically, we demonstrate that inhibitors that can be repurposed to target LZK suppresses LZK kinase-dependent stabilization of MYC and activation of the PI3K/AKT pathway. In vivo preclinical cell line xenograft mouse model demonstrates that targeting LZK will suppress tumor growth. We also demonstrate that several additional compounds potently inhibit LZK and could serve as new therapeutic modalities.

This technology includes anti-PSMA antibody labeled with 177Lu, which has shown to be an effective treatment for prostate cancer. Several small molecules targeting PSMA were also evaluated in prostate cancer patients labeled with betta emitters such as 177Lu. The most common one is 177Lu-PSMA-617 which is under clinical evaluation in many countries. Usual treatment in patients in most clinical trials was composed of up to 3 cycles of 177Lu-PSMA-617.

This technology includes a newly designed, truncated Evans Blue (EB) form which allows labeling with metal isotopes for nuclear imaging and radiotherapy. Unlike previous designs, this new form of truncated EB confers site specific mono-labeling of desired molecules. The newly designed truncated EB form can be conjugated to various molecules including small molecules, peptides, proteins and aptamers to improve blood half-life and tumor uptake, and confer better imaging, therapy and radiotherapy.

Spatial proteomics and transcriptomics are fast-emerging fields with the potential to revolutionize various branches of biology. In the last five years, various multiplex immunofluorescence and immunohistochemistry imaging methods have been developed to stain 5-60 different protein markers in a given tissue. Nonetheless, most of these techniques are iterative and can image a maximum of 3-8 markers in a single cycle, resulting in processing time of several hours to days.

Hyperpolarized magnetic resonance imaging (MRI) is an emerging molecular imaging method for metabolic imaging for detecting cancer, cardiovascular disease, stroke, and traumatic brain injury and monitoring therapy with no Gadolinium or Iron.

GATA-3 is a transcription factor that is highly expressed in normal cells of the mammary luminal epithelium. GATA-3 plays a regulatory role in determining the fate of cells in the mammary gland. Disruption of GATA-3 expression leads to defects in the development of mammary cells, including an inability to differentiate properly into the correct cell type. GATA-3 function is also disrupted in various breast cancer models indicating that GATA-3 has tumor suppressive properties in normal cells.

The National Cancer Institute Cancer Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize mouse epithelial cancer cell lines.