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

Abstract: Engineered proteins, polynucleotides encoding such proteins, and methods of use thereof are provided, which engineered proteins enhance the sensitivity of a cell to IL-2.

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

Abstract: The present disclosure relates generally to compositions and methods for modulating cell surface receptor signaling by specifically recruiting membrane phosphatases, in cis, to a spatial proximity of a natural killer cell receptor (NKR) molecule. More particularly, the disclosure provides novel multivalent protein-binding molecules that specifically bind NKR and antagonize the NKR-mediated signaling through recruitment of a phosphatase activity to dephosphorylate the intracellular domain of the NKR. Also provided are compositions and methods useful for producing such molecules, as well as methods for the treatment of health conditions associated with the inhibition of signal transduction mediated by NKRs.

Abstract: The present disclosure provides methods of producing a modified immune cell responsive to orthogonal cytokine signaling and a modified immune cell produced by said method. The present disclosure further provides a modified immune cell responsive to orthogonal cytokine signaling and methods for treating cancer comprising the modified immune cell.

Abstract: Engineered proteins, polynucleotides encoding such proteins, and methods of use thereof are provided, which engineered proteins enhance the sensitivity of a cell to IL-2.

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 generally to compositions and methods for modulating cell surface receptor signaling by specifically recruiting membrane phosphatases, in cis, to a spatial proximity of a signal regulatory protein ? (SIRP?) molecule. More particularly, the disclosure provides novel multivalent protein-binding molecules that specifically bind SIRP? and antagonize the SIRP?-mediated signaling through recruitment of a phosphatase activity to dephosphorylate the intracellular domain of SIRP?. Also provided are compositions and methods useful for producing such molecules, methods for promoting maturation dendritic cells and for production of vaccine, as well as methods for the prevention and/or treatment of health conditions associated with the inhibition of signal transduction mediated by SIRP? and/or CD47.

Abstract: The present disclosure provides chimeric cytokine receptors comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra). The present disclosure also provides modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, wherein the cell(s) are engineered to express a) interleukin-9 receptor alpha (IL9Ra), or a chimeric cytokine receptor disclosed herein; and b) a chimeric antigen receptor (CAR). The present disclosure further provides a vector (e.g., an oncolytic adenoviral vector) comprising a nucleic acid sequence encoding a cytokine, as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof. Also provided are modified immune cell(s) or precursor cell(s) thereof which are engineered to express a chimeric antigen receptor (CAR), wherein expression of Cullin 5 in the cell(s) is reduced and/or eliminated. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer.

Abstract: The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-12 and interleukin-23. In particular, the disclosure provides novel variants of interleukin-12 subunit p40 with reduced binding affinity to IL-12R?1. Also provided are compositions and methods useful for producing such IL-12p40 polypeptide variants, as well as methods for modulating IL-12p40-mediated signaling, and/or for the treatment of conditions associated with perturbations of signal transduction mediated by IL-12p40.

Abstract: The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-22 (IL-22). In particular, the disclosure provides novel IL-22 polypeptide variants with altered binding affinity to interleukin-10 receptor subunit beta (IL-10R?). Also provided are compositions and methods useful for producing such IL-22 polypeptide variants, as well as methods for modulating IL-22-mediated signaling, and/or for the treatment of conditions associated with the perturbation of signal transduction mediated by IL-22.

Abstract: The present disclosure relates generally to compositions and methods for modulating signal transduction mediated by interleukin-10 (IL-10). In particular, the disclosure provides novel IL-10 polypeptide variants with altered binding affinity to interleukin-10 receptor subunit beta (IL-10R?). Also provided are compositions and methods useful for producing such IL-10 polypeptide variants, as well as methods for modulating IL-10-mediated signaling, and/or for the treatment of conditions associated with the perturbation of signal transduction mediated by IL-10.

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 and to an R-spondin agonist.

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: The present disclosure provides a CAR comprising a tumor antigen binding domain, a transmembrane domain, and an intracellular domain comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra), and modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, engineered to express the CAR. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

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

Abstract: Variant IL-2 proteins and uses thereof are provided. In some embodiments, the IL-2 variant proteins have greater potency for activation of IL-2 signaling pathways in cells lacking CD25 expression, relative to wild-type IL-2.

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