Summary: 
Investigators at the National Institute on Drug Abuse seek co-development partners and/or licensees for collection of mu opioid receptor (MOR) agonists as alternatives for existing compounds.

Description of Technology: 
Although existing opioids are excellent analgesics and useful as positron emission tomography (PET) radiotracers, they come with debilitating side effects. These include addiction, respiratory distress, hyperalgesia, and constipation. Therefore, there is a need for alternatives with lower adverse effects.

Nuclear medicine is the second largest source of medical radiation exposure to the general population after computed tomography imaging. Imaging modalities utilizing nuclear medicine produce a more detailed view of internal structure and function and are most commonly used to diagnose diseases such as heart disease, Alzheimer’s and brain disorders. They are used to visualize tumors, abscesses due to infection or abnormalities in abdominal organs.

The Zbtb7b gene encodes the zinc finger transcription factor ThPOK (also known as cKrox) that promotes CD4 lineage differentiation in immature T cells. CD4+ T cells, also known as “helper” T cells, are critical for long-term immunity against pathogens as well as for promoting CD8+ “effector” T cell and effective B cell responses. ThPOK is needed for the development and functional fitness of CD4+ T cells as well as multiple aspects of the immune response to infection. As such, ThPOK offers a potential target for immune regulation.

Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes tumor infiltrating lymphocytes (TILs) or genetically engineered T cells to attack tumor cells through recognition of tumor-specific antigens. A major hurdle in the development of ACT is the identification and isolation of T cells that recognize antigens that are expressed by tumor cells but not by healthy tissues. Current methods to identify such T cells involve extracting autologous antigen presenting cells (APCs) from patients in an expensive, laborious, and time-consuming process.

There is growing awareness that a wide variety of synthetic and natural compounds that may be present in water sources, such as streams, wells, and ground water, may lead to adverse health effects, including increased cancer risk. Even low concentrations of these compounds are of concern, as they may have biological effects at concentrations of parts per billion or less.

About half of the per capita dose of radiation due to medical exposures is provided by computed tomography (CT) examinations. Approximately 80 million CTs are performed annually in the United States. CT scans most commonly look for internal bleeding or clots, abscesses due to infection, tumors and internal structures. Although CT provides great patient benefit, concerns exist about potential associated risks from radiation doses – especially in pediatric patients more sensitive to radiation.

Human leukocyte antigen (HLA) LOH (LOH) is a known resistance mechanism by which cancers evade T cell receptor-(TCR-)based immunotherapies. This class of therapies includes immune checkpoint inhibition (ICI, e.g., Pembrolizumab), engineered TCR (T cell receptor)-T cell adoptive transfer, tumor infiltrating lymphocytes (TIL), T-cell engagers, and other modalities. Dozens of therapies in this category were developed with many in clinical trials. The resistance mechanism noted here, HLA LOH, causes these therapies to fail.

The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. SARS-COV-2 infects hosts via its spike (S) protein. The S protein contains the receptor binding domain (RBD) that binds to the angiotensin converting enzyme 2 (ACE2) receptor on human cells to facilitate viral entry and infection. There are few therapeutics available for COVID-19 patients that directly target SARS-CoV-2.

Recombinant immunotoxins (RITs) constitute a promising solution to hematologic cancers (e.g., Multiple Myeloma [MM]). RITs are chimeric proteins composed of a targeting domain fused to a bacterial toxin. Upon binding to a cancer cell displaying the target antigen, RITs are internalized, metabolized and the released toxin kills the cell. While highly active and effective, current RITs have short half-lives, requiring them to be used in high concentrations for treatment. At such high concentrations, RITs may show nonspecific activity and kill healthy cells.

Mesothelin (MSLN) is an antigen highly expressed in several human cancers including mesotheliomas, ovarian cancers and pancreatic cancers. As such, human MSLN (hMSLN) is a target for many anti-cancer drugs. Most therapeutics targeting hMSLN do not recognize the mouse isoform of MSLN (mMSLN) and therefore cannot be tested in mouse cancer models.