Natural product-based anti-cancer agents: aza-Englerin analogues

Chemotherapy resistance in a wide array of cancers is often associated with enhanced glucose uptake and dysregulation of the insulin signaling pathway.  Therapeutics capable of inhibiting insulin signaling would be valuable as a stand-alone treatment and for sensitizing resistant tumors to standard chemotherapy regiments.  Researchers at NCI’s Genitourinary Malignancies Branch have synthesized and developed a series of Englerin-A ana

T-Cell Immunotherapy that Targets Aggressive Epithelial Tumors

Metastatic cancers cause up to 90% of cancer deaths, yet few treatment options exist for patients with metastatic disease. Adoptive transfer of T cells that express tumor-reactive T-cell receptors (TCRs) has been shown to mediate regression of metastatic cancers in some patients. Unfortunately, identification of antigens expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies. Thus, it is essential to find novel target antigens differentially expressed in cancer versus normal tissues.

Isotopes of Alpha Ketoglutarate and Related Compounds for Hyperpolarized MRI Imaging

This technology includes 1-13C-ketoglutarate which can be used for imaging the conversion to hydroxyglutarate (HG) or Gln in cancer cells with an IDH1 mutations by hyperpolarized MRI. The ability to detect the status of IDH1 mutations is clinically prognostic for multiple cancers. These exciting observations are limited by two factors, the major one being that the natural abundance of 13C at position C5 overlaps with 1-13C-2-hydroxyglutarate peak, which limits the sensitivity of analysis and prevents simultaneous observations of HG and Gln formation.

LZK and DLK Inhibitors to Target LZK and Suppress MYC Expression, Inhibit AKT Activation, and Promote Cancer Cell Death and Tumor Regression

This technology includes the use of LZK and DLK inhibitors to be used for the treatment of head and neck squamous cell carcinoma (HNSCC) or lung squamous cell carcinoma (LSCC). Specifically, we demonstrate that inhibitors that can be repurposed to target LZK suppresses LZK kinase-dependent stabilization of MYC and activation of the PI3K/AKT pathway. In vivo preclinical cell line xenograft mouse model demonstrates that targeting LZK will suppress tumor growth. We also demonstrate that several additional compounds potently inhibit LZK and could serve as new therapeutic modalities.

Radiotherapy and Imaging Agent-based on Peptide Conjugated to Novel Evans Blue Derivatives with Long Half-life and High Accumulation in Target Tissue

This technology includes a newly designed, truncated Evans Blue (EB) form which allows labeling with metal isotopes for nuclear imaging and radiotherapy. Unlike previous designs, this new form of truncated EB confers site specific mono-labeling of desired molecules. The newly designed truncated EB form can be conjugated to various molecules including small molecules, peptides, proteins and aptamers to improve blood half-life and tumor uptake, and confer better imaging, therapy and radiotherapy.

GATA-3 Reporter Plasmids for Revealing Underlying Mechanisms in Breast Cancer

GATA-3 is a transcription factor that is highly expressed in normal cells of the mammary luminal epithelium. GATA-3 plays a regulatory role in determining the fate of cells in the mammary gland. Disruption of GATA-3 expression leads to defects in the development of mammary cells, including an inability to differentiate properly into the correct cell type. GATA-3 function is also disrupted in various breast cancer models indicating that GATA-3 has tumor suppressive properties in normal cells.

C8166-45 Cells

Summary:

The National Cancer Institute (NCI) seeks licensees for a human T-cell line, C8166-45, transformed by HTLV-1. C8166-45, also known as C63/CRII-2, contains three transcriptionally active proviruses useful for testing biological activities involved in T-cell immortalization and growth.

T Cell Receptor Targeting HPV6 E2 and a Panel of Cos7 Cells Expressing Different HLA Class I Proteins for Use in Validation and Potency Studies

Summary:

The National Cancer Institute (NCI) seeks licensees for this invention comprising (1) a novel T cell receptor (TCR) specific to the E2 protein of Human papillomavirus (HPV) type 6  in the context of the human leukocyte antigen, HLA-B55, and (2) a panel of Cos7 cells expressing different HLA proteins for validation of T cell responses in immunotherapies for low-risk HPV-related diseases such as recurrent respiratory papillomatosis and anogenital condyloma.