Abstract: The present disclosure generally relates to, inter alia, a class of chimeric switch receptors containing an endodomain of an IL-9 receptor, engineered to modulate transcriptional regulation in a ligand-dependent manner. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating gene expression, modulating an activity of a cell, and/or for the treatment of various health conditions or diseases.

Abstract: The present disclosure relates to to compositions and methods relating to cytokine agonists and their engineered polypeptides. The engineered polypeptides have specificity to receptors in immune systems including IL-2/15, Type I IFN and IL-10. The present disclosure also relates to methods for identifying surrogate cytokine agonists and to a system for engineering ligands that can compel formation of non-naturally-occurring cytokine receptor heterodimers. The present disclosure also relates to methods and system for identifying surrogate agonists for cell surface receptors including dimeric and trimeric receptors.

Abstract: De novo designed polypeptides that bind to IL-2 receptor ?c heterodimer (IL-2R?c), IL-4 receptor ?c heterodimer (IL-4R?c), or IL-13 receptor ? subunit (IL-13R?) are disclosed, as are methods for using and designing the polypeptides.

Abstract: De novo designed polypeptides that bind to IL-2 receptor ??c heterodimer (IL-2R??c), IL-4 receptor ??c heterodimer (IL-4R??c), or IL-13 receptor ? subunit (IL-13R?) are disclosed, as are methods for using and designing the polypeptides.

Abstract: The present disclosure generally relates to, inter alia, a class of chimeric switch receptors containing an endodomain of an IL-9 receptor, engineered to modulate transcriptional regulation in a ligand-dependent manner. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating gene expression, modulating an activity of a cell, and/or for the treatment of various health conditions or diseases.

Abstract: Compositions and methods are provided for peptide sequences that are ligands for a T cell receptor (TCR) of interest, in a given MHC context.

Abstract: Wnt signaling antagonist and agonist compositions and methods for their use are provided.

Abstract: High affinity SIRP-? reagent are provided, which (i) comprise at least one amino acid change relative to the wild-type protein; and (ii) have an increased affinity for CD47 relative to the wild-type protein. Compositions and methods are provided for modulating phagocytosis in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity SIRP? reagent, which blocks the physiological binding interaction between SIRP? and its ligand CD47.

Abstract: Wnt signaling agonist compositions and methods for their use are provided. Wnt signaling agonists of the invention comprise a frizzled binding moiety, which is fused or conjugated to an LRP5 or LRP6 binding moiety.

Abstract: Provided herein, inter alia, are human interleukin-2 (IL-2) muteins or variants thereof. In particular, provided herein are IL-2 muteins that have a decreased binding capacity for IL-2R?. Such IL-2 muteins are useful, for example, as IL-2 partial agonist in applications where reduction or inhibition of one or more IL-2 and/or IL-15 functions is useful (e.g., in the treatment of autoimmune diseases or conditions). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

Abstract: Engineered orthogonal cytokine receptor/ligand pairs, and methods of use thereof, are provided.

Abstract: Provided herein, inter alia, are human interleukin-2 (IL-2) muteins or variants thereof. In particular, provided herein are IL-2 muteins that have a decreased binding capacity for IL-2R?. Such IL-2 muteins are useful, for example, as IL-2 partial agonist in applications where reduction or inhibition of one or more IL-2 and/or IL-15 functions is useful (e.g., in the treatment of autoimmune diseases or conditions). Also provided are nucleic acids encoding such IL-2 muteins, methods of making such IL-2 muteins, pharmaceutical compositions that include such IL-2 muteins and methods of treatment using such pharmaceutical compositions.

Abstract: Engineered T cell receptor (TCR) sequences, cells expressing such sequences and methods of use thereof are provided. The engineered receptors are mutagenized in vitro, and selected for target activation potency in combination with selection for a pMHC affinity that is sufficiently low to reduce off-target cross-reactivity.

Abstract: Wnt signaling antagonist and agonist compositions and methods for their use are provided.

Abstract: Compositions and methods are provided for the development and screening of antibody-based binding regions (ABR) that mimic T cell receptor specificity (TCRm). The TCRm-ABR of the disclosure are developed to specifically bind to the combination of an MHC antigen and peptide, and to substantially lack binding to the MHC in the absence of the cognate antigen.

Abstract: Provided herein are Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR) constructs and related compositions, kits, methods of use and methods of production. REULR constructs comprise a variable domain heavy chain antibody (VHH) specific for a E3 Ubiquitin Ligase, and a VHH specific for a target protein, where in the E3 Ubiquitin Ligase and the target protein are different. REULR constructs described here target proteins associated with many maladies, but especially cancer.

Abstract: Engineered orthogonal cytokine receptor/ligand pairs, and methods of use thereof, are provided.

Abstract: Novel human interleukin-2 (IL-2) muteins or variants thereof, and nucleic acid molecules and variants thereof are provided. Methods for producing these muteins as well as methods for stimulating the immune system of an animal are also disclosed. In addition, the invention provides recombinant expression vectors comprising the nucleic acid molecules of this invention and host cells into which expression vectors have been introduced. Pharmaceutical compositions are included comprising a therapeutically effective amount of a human IL-2 mutein of the invention and a pharmaceutically acceptable carrier. The IL-2 muteins can be used in pharmaceutical compositions for use in treatment of cancer and in stimulating the immune response.

Abstract: Engineered synthekines and methods of use thereof are provided.

Abstract: R-spondin (RSPO) surrogate compositions and methods for their use are provided. RSPO surrogates of the invention comprise (i) a specific binding domain for Ring Finger Protein 43 (RNF43) or Zinc and Ring Finger Protein 3 (ZNRF3) and (ii) a cell targeting domain More specifically, wherein the specific binding domain for RNF43 or ZNRF3 is an antibody fragment, and wherein the cell targeting domain is a cytokine.