Development of successful HIV vaccine immunogens continues to be a major challenge. Although gp120 was identified as having significant potential as a vaccine immunogen, attempts to elicit broadly neutralizing antibodies using recombinant gp120 failed. The highly flexible gp120 may present numerous conformations to the humoral immune system that are not found on the viral spike.
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.
The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers. The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.
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.
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.
The National Cancer Institute, Cancer and Inflammation Program seeks parties interested in collaborative research to further co-develop inhibitors of STAT proteins for the treatment of cancer.
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.
The National Cancer Institute, Nanobiology Program seeks parties interested in collaborative research to co-develop engineered molecules therapies.
The National Cancer Institute's Laboratory of Cell Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of DKK1 to treat abnormal pigmentation of the skin or to regulate hair growth.
Natural killer T cells (NKT) are a unique lymphocyte population that has T-cell and NK cell functional properties in order to rapidly elicit an immune response. alpha-galactosylceramide (alpha-GalCer) is a potent NKT stimulator and induces of IFN-gamma release to promote immunity against tumors and infectious agents. Humans have natural antibodies against alpha-galactose, which may be one of the reasons why the human clinical trials of alpha-GalCer or KRN7000 were not very successful.