Investigators at the National Institutes of Health (NIH) have discovered compounds that have potential as novel anti-androgen therapeutics. The immunophilin protein FKBP52 is part of a protein complex that helps fold the androgen receptor (AR) protein, a target for treating prostate cancer, and enhances its activity. Disruption of the FKPB52-AR interaction greatly reduces the activity of the AR.
Adoptive cell therapy (ACT) using genetically engineered T-cell receptors (TCRs) is a promising cancer treatment. These TCRs target genetic mutations unique to patients and play an important role in tumor regression. However, mutation-reactive T-cells and their TCRs can be difficult to identify and isolate from patients. Therefore, we need more efficient methods of isolating mutation-reactive T-cells for use with ACT.
A Sensitive, High Throughput Pseudovirus-Based Papillomavirus Neutralization Assay for HPV 16 and HPV 18
Human Papilloma Viruses (HPV) is a very common virus; nearly 80 million people—about one in four—are currently infected in the United States. HPV is a group of more than 150 related viruses. Each HPV virus in this large group is given a number which is called its HPV type. HPV is named for the warts (papillomas) some that HPV types can cause. Some other HPV types can lead to cancer, especially cervical cancer.
The National Cancer Institute’s Protein Expression Laboratory seeks parties to co-develop dual luminescent/fluorescent cancer biomarkers.
In research settings, visualization of tumors or tumor cells is often done using either bioluminescence or fluorescence. However, both of these methods have shortcomings: bioluminescence is not sensitive enough to sort individual tumor cells, and fluorescence cannot be used effectively to view internal tumors and is best used with surface tumors.
Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.
Diazeniumdiolates comprise a diverse class of NO-releasing compounds and materials that are known to exhibit sufficient stability to be useful as therapeutics.
HMGN polypeptides belong to the high mobility group (HMG) family of chromosomal binding peptides. HMGN polypeptides typically function inside the cell nucleus to bind to DNA and nucleosomes and regulate the transcription of various genes. HMGN polypeptides also can be released by peripheral blood mononuclear cells. However, the extracellular release of a HMGN polypeptide initiates activation of the immune system. Therefore, it has potential use as a biological therapeutic for stimulating an immune response.
Metastatic cancers are the cause of 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 that are expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies.
The National Cancer Institute Laboratory of Molecular Biology seeks parties for collaborative research to co-develop and commercialize antibody drug/toxin conjugates as liver cancer therapy and diagnostics.
Despite recent breakthroughs in cancer immunotherapy, T-cell based therapies achieve limited efficacy in solid tumors. Immunosuppression, antigen escape and physical barriers to entry into solid tumors are issues faced. Identifying regulators in T-cell dysfunction remains challenging due to limitations of current screening platforms.