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Developing computer systems that can recognize and locate image features associated with disease is a challenge for developing fully-automated and high precision computer assisted diagnostics. Joint learning of language tasks in association with vision tasks (association of image features with text annotation) adds an additional level of challenge.  Furthermore, scaling-up approaches from small to large datasets presents additional issues, particularly related to medical images.

Epidermal growth factor receptor variant III (EGFRvIII) is a variant of EGFR that is an excellent target for immunotherapy because of its expression in cancer cells and not in normal cells. 

The tumor microenvironment (TME) is a complex mixture of cell types whose interactions affect tumor growth and clinical outcome. Recent studies using fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (RNAseq) to elucidate tissue composition and cell-cell interactions in the TME led to improved biomarkers of patient response and new treatment opportunities. However, the use of FACS is limited to simultaneously measuring the expression of a few protein markers, whereas the use of single-cell RNAseq has been limited due to cost and scarcity of fresh tumor biopsies.

Castrate-resistant prostate cancer (CRPC) is characterized by androgen-independent cancer cells that have adapted to the depletion of hormones and continue to grow. Abnormal androgen receptor signaling is known to drive advanced castrate-resistant prostate cancer.

Mutation of amino acid 61of the neuroblastoma rat sarcoma viral oncogene homologue (NRAS) is a known driver of oncogenesis in melanoma. Glutamine (Q) to lysine (K) mutation at this position of NRAS is prevalent in approximately 10% of all melanoma cases and associated with aggressive tumors and low patient survival. Therefore, Q61K mutated NRAS is an important candidate for targeted therapies, including cellular immunotherapy. 

Neurofibromatosis type 1 (NF1) is a genetic disorder affecting 1 per 3000 individuals on average. Patients develop a variety of developmental benign and malignant pathologies. The most common tumors associated with NF1 are peripheral sheath tumors, including neurofibromas, optical gliomas, and malignant peripheral nerve sheath tumors.

The retinal pigment epithelial cells (RPE) make up a polarized monolayer in the vertebrate eye that separates the neural retina from the choroid, and performs a crucial role in retinal physiology by forming a blood-retinal barrier and closely interacting with photoreceptors to maintain visual function.  Many ophthalmic diseases, such as age-related macular degeneration, are associated with a degeneration or deterioration of the RPE. 

Chimeric antigen receptors (CARs) are hybrid proteins consisting of an antibody binding fragment fused to protein signaling domains that cause T-cells which express the CAR to become cytotoxic.  Once activated, these cytotoxic T-cells can selectively eliminate the cells which they recognize via the antibody binding fragment of the CAR.  By engineering a T-cell to express a CAR that is specific for a certain cell surface protein, it is possible to selectively target those cells for destruction.  This is a promising new therapeutic approach known as adoptive cell therapy.

Researchers at the NCI  Laboratory of Molecular Theranostics and the Molecular Imaging Program have developed a new method to modify, isolate and remove a single chemically-labeled molecule or a cluster of proteins associated with the chemically-labeled protein. The chemical label can be an antigen-antibody complex. This discovery is based on the mechanism of photo-immunotherapy (PIT).

Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.