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.

High-Affinity Rabbit Monoclonal Antibodies for Cancer Treatment

Mesothelin is a cell surface protein that is highly expressed in aggressive cancers, such as malignant mesothelioma, ovarian cancer and pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma, bile duct carcinoma and gastric cancer.  Because of this selective expression, mesothelin is an excellent candidate for targeted therapeutics, such as monoclonal antibodies (mAbs) and chimeric molecules.  Current anti-mesothelin therapeutic mAb candidates bind to an epitope in Region I of mesothelin.  Unfortunately, Region I contains the interaction site MUC16/CA125, a mesothe

Analogues of Modafinil for treating sleep and attention disorders

Modafinil has attracted attention for the treatment of cognitive dysfunction in disorders such as attention-deficit/hyperactivity disorder (ADHD) as well as cocaine and methamphetamine dependence.  However, modafinil has relatively low affinity for binding to the dopamine transporter (DAT) to block dopamine reuptake, and is water-insoluble, thus requiring large doses to achieve pharmacological effects.

PARP Inhibitor and NO-Donor Dual Prodrugs as Anticancer Agents

Poly-ADP ribose polymerase-1 (PARP-1) is a critical enzyme involved in DNA repair.  The inhibition of PARP has emerged as a promising strategy in cancer therapy.  Numerous PARP inhibitors have been developed and advanced into clinical trials, both for use as single agents in specific patient populations and as combination therapies with various chemotherapeutics.  The induction of strand break damage to DNA, as has been demonstrated in cancer cells treated with O2-arylated diazeniumdiolates, coupled with inhibition of DNA repair by PARP inhibitors, represents a novel rational