Main Menu

Antibody drug conjugates (ADC) can demonstrate high efficacy as cancer therapeutics, however, much more can be done to improve their efficacy and safety profile. Site-specific antibody drug conjugation is a promising way to do this. Scientists at the NCI’s Laboratory of Experimental Immunology have identified a fully human monoclonal antibody, m860, that binds to cell surface-associated Her2 with affinity comparable to that of Trastuzumab (Herceptin) but to a different epitope.

Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual''s innate and adaptive immune system to fight against specific diseases, including cancer with fewer side-effects and more specific anti-tumor activity in individual patients. T cell receptors (TCRs) and Chimeric Antigen Receptors (CARs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response to destroy abnormal cells.

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.

One major challenge in the development of effective cancer therapies is a lack of universal, cancer specific markers in target cells. The current standard therapies rely on surgery, chemotherapy, and radiation therapy. Such procedures lead to a population of resistant cancer cells that makes further applications of chemotherapy/radiation therapy ineffective. Additionally, the systemic application of chemotherapy lacks specificity and has  off-target systemic effects that lead to adverse side effects.

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.

Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes.  NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability.  For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments. 

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.