Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of T1D epitopes in the context of a Class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding those MAPPs. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the T1D epitopes presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and PD-L1 polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present disclosure provides antigen presenting polypeptide comprising a TGF-? MOD that is reversibly masked and acts as a TGF-? receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, Type 1 Diabetes (T1D) associated epitope containing polypeptides. The antigen-presenting polypeptides and their T1D-associated epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of T1D.

Abstract: The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) that comprise a TID-associated peptide epitope and a reversibly masked TGF-? peptide capable of acting as an agonist of cellular TGF-? receptors. The MAPPs are capable of presenting the TID-associated peptide epitope in the context of a Class II MHC receptor to T cells. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding those MAPPs. MAPPs of the present disclosure are useful for selectively modulating activity of a T cells having T cell receptors that recognize the TID epitopes presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have TID.

Abstract: The present disclosure provides antigen presenting polypeptide comprising a TGF-? MOD that is reversibly masked and acts as a TGF-? receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, epitope containing polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides comprising one or more chemical conjugation sites, as well as cells genetically modified with the nucleic acids. The antigen-presenting poly peptides and their epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of diseases and disorders including autoimmune diseases, allergies, GVHD, HGVD, and metabolic disorder.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (“T-Cell-MMPs”) comprising an immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”) and a location for covalently attaching a molecule that can serve as an epitope, such as an epitope peptide. Once the epitope molecule is attached the resulting T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for IL-2R, to the T-cells in an epitope selective/specific manner, and accordingly, for modulating an immune response in an individual.

Abstract: The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) that comprise a peptide epitope and a reversibly masked TGF-? peptide capable of acting as an agonist of cellular TGF-? receptors. The MAPPs are capable of presenting the peptide epitope in the context of a Class II MHC receptor to T cells. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. The MAPPs are useful for selectively modulating activity of a T cells having T cell receptors that recognize the epitope presented by the MAPP. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including autoimmune diseases, graft vs. host disease, host vs. graft disease, and/or allergies.

Abstract: The present disclosure provides T-cell modulatory polypeptides (TMPs) comprising an AI peptide epitope, MHC class II polypeptides, one or more immunomodulatory polypeptides, a TGF-? polypeptide, and a masking polypeptide. A TMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have an autoimmune disease.

Abstract: The present disclosure provides T-cell modulatory polypeptides (TMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, one or more immunomodulatory polypeptides, a TGF-? polypeptide, and a masking polypeptide. A TMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present disclosure provides T cell modulatory polypeptides (T-Cell-MPs) comprising a chemical conjugation site at which a KRAS epitope has been conjugated and at least one immunomodulatory polypeptide sequence that may be selected to exhibit reduced binding affinity to its cognate co-immunomodulatory polypeptide. The T-Cell-epitope conjugates are useful for modulating (e.g., increasing proliferation or cytotoxic activity) the activity of T cells specific to the conjugate epitope, and accordingly for use as therapeutics. The T-Cell-epitope conjugates find use in treating a variety of cancers associated with KRAS.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a ?2 microglobulin polypeptide), a peptide that presents an epitope to a T-cell receptor, and a tumor-targeting polypeptide. A TMMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Abstract: The present disclosure provides Multimeric Antigen Presenting Polypeptides (MAPPs) for the presentation of KRAS antigens in the context of a class I MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids. MAPPs of the present disclosure are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers.

Abstract: The present disclosure provides Transforming Growth Factor Beta (TGF-?) polypeptide constructs and complexes that find use in, for example, therapeutic treatment of diseases including autoimmune diseases and metabolic diseases and disorders. Also described are nucleic acids that encode the constructs and complexes and methods of preparing the constructs and complexes in cell-based expression systems.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising an autoimmune dis-ease-associated-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have an autoimmune disease.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides (TMMPs) comprising a type 1 diabetes (T1D)-associated peptide epitope, MHC class II polypeptides, and one or more immunomodulatory polypeptides. A TMMP of the present disclosure is useful for modulating activity of a T cell. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have T1D.