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.

Nitric Oxide Based Therapeutics for the Treatment of Lung Cancer

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. 

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.

Multifunctional RNA Nanoparticles as Cancer and HIV Therapeutics

The promise of RNA interference based therapeutics is made evident by the recent surge of biotechnological drug companies that pursue such therapies and their progression into human clinical trials. The present invention discloses novel RNA  and RNA/DNA nanoparticles including  multiple siRNAs, RNA aptamers, fluorescent dyes, and proteins. These RNA nanoparticles are useful for various nanotechnological applications.

Novel Immunotherapy for Cancer Treatment: Chimeric Antigen Receptors Targeting CD70 Antigen

Scientists at the NCI's Surgery Branch have developed anti-CD70 chimeric antigen receptors (CARs) to treat cancers. CD70 is an antigen that is expressed on a variety of human cancers such as renal cell carcinoma, glioblastoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. The anti-CD70 CARs are hybrid proteins consisting of a receptor portion that recognizes CD70 antigen, and intracellular T cell signaling domains selected to optimally activate the CAR expressing T cells.

Cancer Therapeutic based on Stimulation of Natural Killer T-cell Anti-tumor Activity

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.

Improved Production of Prenylated Protein in Insect Cells

KRAS and other Ras-family enzymes are an important component of over 30% of human cancers, however, no effective therapeutics targeting Ras or Ras-driven cancers are currently available.  The production of Ras proteins in vitro is required for the identification and characterization of Ras targeting drugs.  An important step in producing the Ras protein involves prenylation of the C-terminus of the protein via farnesyltransferase, a modification that does not occur in prokaryotic organisms.  Previous attempts to generate properly processed Ras in eukaryotic cells has