The National Cancer Institute''s Laboratory of Cell Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize bodipy conjugated tyrosine kinase inhibitors that are currently used in the clinic for the treatment of CML or gastric cancers. We are also interested in evaluating third generation tyrosine kinase inhibitor derivatives as modulators of ABC drug transporters to improve the efficiency of chemotherapy in animal (mouse) model system.

Adoptive cell transfer (ACT) uses tumor infiltrating lymphocytes (TILs) that recognize unique antigens expressed by cancer cells (“neoantigens”). Neoantigen specific TIL administration in patients has resulted in long term regression of certain metastatic cancers. However, one of the challenges of ACT and engineered T cell receptor (TCR) therapies more broadly, is the identification and isolation of these mutation specific TILs and TCRs. Only a fraction of TILs in a given patient is known to be tumor reactive, while the majority are not useful for cell therapy.

Many chemotherapeutic agents cause significant cytotoxicity to non-cancer ("normal") cells, resulting in undesirable side-effects and often limiting the dose and/or duration of chemotherapy that can be administered to a patient.

High expression of CD47, a cell surface receptor on several types of cancer cells, has been identified as a ‘don’t eat me signal’ that inhibits their killing by macrophages or NK cells. Conversely, the CD47 antibody B6H12 that blocks SIRPα binding enhances macrophage-dependent clearance of tumors in several mouse models, although others have shown that such clearance can be independent of SIRPα signaling.

It is well known that overactive Ras signaling is linked to many forms of cancer, and despite intensive efforts worldwide to develop effective inhibitors of Ras, to date there is no anti-Ras inhibitor in clinical use.

Medical imaging is an important resource for early diagnostic, detection, and effective treatment of cancers. However, the screening and review processes for radiologists have been shown to overlook a certain percentage of potentially cancerous image features. Such review errors may result in misdiagnosis and failure to identify tumors. These errors result from human fallibility, fatigue, and from the complexity of visual search required.

One form of adoptive T cell therapy (ACT) consists of harvesting tumor infiltrating lymphocytes (TIL), screening and isolating TIL which display tumor antigen-specific T-cell receptors (TCR), expanding the isolated T cells in vitro, and reinfusing them into the patient for treatment. While highly active in the treatment of certain cancers (e.g., melanoma), current methods used to produce cancer-reactive T cells require significant time and may not adequately identify the desired TCRs which bind cancer targets.

Pulmonary surfactant plays a critical role in preventing alveolar collapse by decreasing surface tension at the alveolar air-liquid interface. Surfactant deficiency contributes to the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), common disorders that can afflict patients of all ages and carry a mortality rate greater than 25%. Excess surfactant leads to pulmonary alveolar proteinosis.

The chemokine receptor, CCR4 is a seven transmembrane G protein-coupled cell surface receptor molecule with selective expression on cells of the hematopoietic system. In adult T cell leukemia (ATL), the cell-surface expression of CCR4 on leukemic cells has been found to be nearly universal. Therefore, a CCR4-directed chimeric antigen receptor (CAR) -cell may provide an effective therapeutic against ATL.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children with approximately 3,250 new cases occurring per year in the United States. About 20% of cases are refractory to current treatment protocols and there is a desperate need for targeted therapies that do not result in adverse side effects such as cognitive impairment.