B-cell Surface Reactive Antibodies for the Treatment of B-Cell Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes.  Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST).  However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients.  Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.

Biomarker signature development: microRNAs for biodosimetry

Alterations in microRNAs (miRNAs), a type of small non-coding RNAs, have been reported in cells/tumors subjected to radiation exposure, implying that miRNAs play an important role in cellular stress response to radiation. NCI researchers evaluated small non-coding RNAs, long non-coding RNAs (lncRNA), and mRNA, as potential non-invasive biomarkers for radiation biodosimetry. While the use of miRNAs as radiation biomarkers has been reported, the integrated use of miRNAs, mRNAs and lncRNAs to accurately determine radiation doses is novel and has not been published.

Metastatic ovarian cancer mouse models and cell lines for preclinical studies

The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value.

T cell tuning molecules that modify the immune response to cancer cells

Researchers at NIH/NICHD have identified approximately 200 proteins as candidate molecules (leads) that “fine tune” T cell receptor (TCR) signaling. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) seeks partners to collaborate on in vitro studies to validate these potential immunomodulators and to conduct in vivo studies in a murine cancer model to determine the effects of ligands (e.g. antibodies) to the proteins to determine their effect on the immune response to cancer cells.

Use of Cucurbitacins and Withanolides for the Treatment of Cancer

Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2). 

Hydrocarbon Stapled Peptides that Inhibit the Linear Ubiquitin Chain Assembly Complex (LUBAC) for the Therapy of the Activated B Cell-like (ABC) Subtype of Diffuse Large B Bell Lymphoma (A Type of Non-Hodgkin’s Lymphoma)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma and consists of three subtypes: activated B-cell (ABC), germinal center B-cell (GBC), and primary mediastinal B-cell (PMB). Despite advances in the front-line therapy for DLBCL, approximately one-third of patients will relapse. Substantially worse outcomes have been reported for patients diagnosed with ABC DLBCL and treated with standard chemoimmunotherapy, suggesting the need for novel strategies that improve treatment outcomes.

Mouse Xenograft Model for Mesothelioma

The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas.  Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.