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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.

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. 

The National Cancer Institute, Nanobiology Program seeks parties interested in collaborative research to co-develop engineered molecules therapies.

Fms-like tyrosine kinase 3 (FLT3) is a cytokine receptor which belongs in the receptor tyrosine kinase class III.  FLT3 is expressed on the surface of many hematopoietic progenitor cells and plays an important role in hematopoietic stem/progenitor cell survival and proliferation.  It is often overexpressed in acute lymphoblastic leukemia (ALL) and is frequently mutated in acute myeloid leukemia (AML).  The standard therapies for ALL and AML are still suboptimal for many patients, especially pediatric.  In certain types of ALL or AML, the survival rate is less than 40 and

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

The National Cancer Institute is seeking parties interested in licensing human monoclonal antibodies (mAbs) that bind to death receptor 4 ("DR4").

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

Tumor necrosis factor receptor type 2 (TNFR2)-expressing regulatory T cells (Tregs), present in the tumor microenvironment, play an important role in tumor immune evasion. TNFR2 plays a crucial role in stimulating the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses. In addition to its expression on Tregs, TNFR2 is also known to be overexpressed on some types of tumors and the survival and growth of these tumor cells is promoted by ligands of TNFR2.

Polo-like kinase 1 (Plk1) is a critical protein involved in regulation of mitosis, and aberrant expression of this kinase is found in various cancer types.  Inhibition of Plk1 is currently being pursued in pre-clinical drug development for novel anti-cancer therapeutics.  Plk1 contains an allosteric domain, known as the polo-box domain (PBD), that is responsible for localizing the kinase domain to mitotic structures through protein-protein interactions.  

Topoisomerase 1 (TOP1) is an essential enzyme that plays a critical role in DNA transcription and replication. TOP1 inhibitors are a known class of anti-cancer agents that work to interrupt DNA replication in cancer cells, causing cell death. Since the discovery of the TOP1 inhibitor camptothecin (CPT) from plant extracts more than 60 years ago, two CPT analogs (irinotecan and topotecan) were approved by the FDA for cancer treatment. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme involved in DNA repair created when TOP1 is inhibited.