Hydrocarbon Stapled Peptides that Inhibit the Linear Ubiquitin Chain Assembly Complex (LUBAC) for the Therapy of the Activated B Cell-like (ABC) Subtype of Diffuse Large B Bell Lymphoma (A Type of Non-Hodgkin’s Lymphoma)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma and consists of three subtypes: activated B-cell (ABC), germinal center B-cell (GBC), and primary mediastinal B-cell (PMB). Despite advances in the front-line therapy for DLBCL, approximately one-third of patients will relapse. Substantially worse outcomes have been reported for patients diagnosed with ABC DLBCL and treated with standard chemoimmunotherapy, suggesting the need for novel strategies that improve treatment outcomes.

Engineered Biological Pacemakers

The National Institute on Aging's (NIA) Cellular Biophysics Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize biological pacemakers.

A common symptom of many heart diseases is an abnormal heart rhythm or arrhythmia. While effectively improving the lives of many patients, implantable pacemakers have significant limitations such as limited power sources, risk of infections, potential for interference from other devices, and absence of autonomic rate modulation.

Novel Cancer Immunotherapy: A T Cell Receptor That Specifically Recognizes Common KRAS Mutations

Several malignancies associated with a poor prognosis such as lung, pancreatic and colorectal cancers frequently harbor constitutively active KRAS mutants, which play a pivotal role in oncogenesis.  Currently, there are no potentially curative treatments against most mutant KRAS harboring cancers once they become metastatic and unresectable.  Despite intensive efforts to develop potent mutant KRAS inhibitors, none have shown a significant improvement to patients.

Improved Personalized Cancer Immunotherapy

Scientists at NIH have identified a process to select highly tumor-reactive T cells from a patient tumor sample based on the expression of four specific T cell surface markers: programmed cell death protein 1 (PD-1; CD279), 4-1BB (CD137), T cell lg-and mucin-domain-containing molecule-3 (TIM-3), and/or lymphocyte activation gene 3 (LAG-3). After this enriched population of tumor fighting T cells, primarily tumor infiltrating lymphocytes (TIL), is selected and expanded to large quantities, it gets re-infused into the patient via an adoptive cell transfer (ACT) regimen.

Brain endothelial reporter cells

Aberrant function of the WNT-b-catenin pathway is a common underlying cause of tumorigenesis.  Despite the attractiveness of the WNT-b-catenin pathway as a therapeutic target, WNT dependent cell signaling is also crucial for normal tissue development, and is ubiquitous in all organs.  As a result, WNT-b-catenin pathway inhibitors cause many side effects and fail to meet FDA safety standards.  A more targeted approach is needed to develop safe and effective WNT signaling inhibitors.

Thalidomide Analogs that Inhibit Inflammation and Angiogenesis

Thalidomide and its close analogs (lenalidomide and pomalidomide) are widely used to treat a variety of diseases, such as multiple myeloma and other cancers as well as the symptoms of several inflammatory disorders. However, thalidomide is known for its teratogenic adverse effects when first clinically introduced in the 1950s, and is associated with drowsiness and peripheral neuropathy. Hence, there is intense interest to synthesize, identify and develop safer analogs.