This technology includes mouse models that express versions of mouse cryopyrin protein containing mutations associated with human CAPS disease. We engineered mutations associated with three specific CAPS phenotypes (familial cold autoinflammatory syndrome (FCAS); Muckle-Wells syndrome (MWS); and neonatal onset multisystem inflammatory disease (NOMID)) into the mouse cryopyrin gene (called Nlrp3) to examine the roles of IL-1 β and related cytokines, and better characterize inflammasome functions.

This technology includes the use of genetic markers to predict the response of patients, particularly children with systemic juvenile idiopathic arthritis (sJiA), to anakinra treatment. Anakinra is a human recombinant IL-1 RA used in treating sJiA, a severe childhood inflammatory disease where early and effective treatment is essential for better long-term outcomes. Through the analysis of 38 children with sJiA treated with anakinra, specific sJiA-associated SNPs (single nucleotide polymorphisms) were identified as predictors of therapeutic failure, with a significant odds ratio of 17.3.

This technology includes the development of a mouse line capable of producing single-chain antibodies (nanobodies). Nanobodies, identified initially from Camelidae (including llamas and camels) but also found in cartilaginous fish, consist of a single variable heavy chain domain (VHH) that binds to specific epitopes. Nanobodies have equivalent binding specificity to antigens as antibodies but are more heat- and detergent-stable.

This technology includes a number of dimeric RGD peptides which been developed and labeled with various PET isotopes (1BF, 68Ga, and 64Cu) for imaging integrin expression in cancer, inflammation, rheumatoid arthritis, myocardial infarct, stroke and traumatic injury. A number of these peptides have been translated into clinic for diagnosis and therapy response monitoring.

Disorders of adult beta-globin synthesis, which include sickle cell disease (SCD) and beta-thalassemia, are the most common monogenic disorders in the world. While the curative potential of bone marrow transplantation has been demonstrated, this approach is limited to a small fraction of affected patients due to the requirement for an HLA-matched donor, the highly specialized approach that requires critical infrastructure, and the high cost.

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.

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.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. standard treatment for HCC is not suitable for a large proportion of liver cancer patients. As a result, alternative treatments are needed. Chimeric antigen receptor (CAR) T cell therapy is a promising alternative approach selectively targets targeting tumors via tumor-specific antigens. However, to date, no effective CAR T cell therapy exists for HCC.