K-Ras is the most frequently mutated oncogene in human cancer. Disclosed herein are compositions and methods for modulating K-Ras and treating cancer.

Provided herein are methods of treating cancer using agonistic antibodies that specifically bind to immunostimulatory receptors, wherein the antibodies are administered in an amount and/or frequency sufficient to achieve and/or maintain a receptor occupancy of less than about 80%, for example, a receptor occupancy of about 20% to about 80%. Also provided are methods of determining human doses for such agonistic antibodies, and methods for monitoring receptor occupancy of the agonistic antibodies in order to maintain effective antibody levels in, e.g., human patients. Also provided are methods of measuring soluble OX40 in a subject. Also provided are methods of treating cancer, comprising administering to the subject an effective amount of each of an anti-OX40 antibody and an anti-PD-1 antibody.

The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that modulate microglia activation. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to modulate microglia activation. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired levels of potency to modulate microglia activation.

The invention relates to inhibitors of CDK12 (cyclin-dependent kinase 12), and there use in the treatment or prevention of a disorder in a subject caused by the generation of repeat expansion transcripts.

The present invention relates to compositions and methods of use of anti-ADAMTS13 autoantibodies and fragments thereof. In one aspect, the invention includes a composition comprising an isolated anti-ADAMTS13 autoantibody or fragment thereof. In other aspects, methods are described for generating an in vivo model of thrombotic thrombocytopenic purpura (TTP) comprising introducing at least one anti-ADAMTS13 autoantibody or fragment thereof into a model organism and identifying an anti-autoimmune reagent for treating TTP.

Methods and computer systems are described herein for identifying small molecules that bind to selected RNA structural features (e.g., to RNA secondary structures). Also described are compounds and compositions that modulate RNA function and/or activity.

A Ligand-guided-Selection (LIGS) method for identifying highly specific aptamers against a predetermined antigen of a target is provided. LIGS uses a stronger and highly specific bivalent binder (e.g. an antibody) interacting with its cognate antigen to displace specific aptamers from an enriched SELEX pool. Elution of the displaced aptamers provides aptamers that are specific to the predetermined antigen.

A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.

The present invention relates to a pharmaceutical composition for preventing or treating hypertrophic scars. The present inventors have found that the inhibition of expression of TXNDC5, PRRC1, S100A11, Galectin 1, Filamin A, eIF-5A, Annexin A2, and FABP5 can be a new target for improving and treating hypertrophic scars. In the present invention, TXNDC5-, PRRC1-, S100A11-, Galectin 1-, Filamin A-, eIF-5A-, Annexin A2-, and FABP5-specific siRNAs were constructed to determine the probability of treating the hypertrophic scars. As a result, the knockdown of the protein or a gene encoding the protein induces apoptosis in the hypertrophic scars and reduces collagen expression, which can be very useful in treating wounds.

Provided by the present disclosure are fluorescent proteins that can detect kinase activity. The fluorescent proteins of the present disclosure have us in, for example, detecting kinase activity in any eukaryotic cell.