Compositions and methods for the treatment of malignancy are disclosed.

Provided are high-throughput screens for biologically active modulators of a target enzyme that mimic or recreate natural processes of diversification and selection. In some embodiments, the platform comprises one or more expression systems including without limitation (i) a two-hybrid system that, when expressed in a cell, links survival of the cell to the modulation of a therapeutic target, and (ii) a metabolic system that enables the biosynthesis of structurally varied modulators of the therapeutic agent.

Provided is a bi-specific fusion polypeptide comprising a fynomer sequence that binds to interleukin-17a (IL-17a) and is conjugated to an antibody or subsequence thereof that binds to interleukin-6 receptor (IL-6R). The fusion polypeptide can bind to both IL-17a and IL-6R thereby suppresses, reduces, decreases, inhibits or blocks both IL-17a and IL-6R activities.

Compositions and methods for the treatment of malignancy are disclosed.

A tropomyosin receptor kinase (Trk) antagonist having a compound of formula (I) or a pharmaceutically acceptable salt thereof,

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wherein R1 is CH.sub.3, R2 is OCH.sub.3, R3 is SO.sub.2N(CH.sub.3).sub.2, and R4 is H; or R1 is CH.sub.3, R2 is OH, R3 is SO.sub.2N(CH.sub.3).sub.2, and R4 is H.

The present disclosure provides compositions and methods for making and using engineered killer phagocytic cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, the chimeric receptor is encoded by a recombinant nucleic acid.

The present invention relates to a Truncated isoform of Anaplastic Lymphoma Kinase (TALK). Expression of this isoform is associated with malignancy and with responsiveness to ALK inhibitors. Detection of the isoform may be used in diagnostic and therapeutic methods. Because it arises as a result of variant transcription rather than genetic rearrangement, its presence would be undetected by genomic testing.

Provided herein are ABL1 fusion nucleic acid molecules and polypeptides, methods related to detecting ABL1 fusion nucleic acid molecules and polypeptides in cancer, as well as methods of treatment and uses related thereto. Detection of an ABL1 fusion nucleic acid molecule or polypeptide can be used to identify individuals that may benefit from treatment with an anti-cancer therapy.

The present invention relates to methods of designing kinase mutants for reprogramming the sensitivity of a target kinase to some specific inhibitors, methods of reprogramming the sensitivity of a target kinase to some specific inhibitors, wherein those kinase inhibitors have little or no affinity for the wild-type target kinase, vectors or cells expressing said mutated kinases, composition and uses thereof for the prevention and/or treatment of a disease or disorder, in particular cancer.

In alternative embodiments, provided are self-activating Frster resonance energy transfer (saFRET) biosensors, and methods for making and using them. In alternative embodiments, provided are self-activating FRET (saFRET) biosensors, and methods that couple FRET and sequencing (FRET-Seq) to integrate random mutagenesis, fluorescence-activated cell sorting (FACS), and next-generation sequencing (NGS) to screen and identify sensitive biosensors from large-scale libraries directly in mammalian cells, utilizing the design of saFRET biosensors as provided herein.