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 polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a ?2 microglobulin polypeptide), and a peptide that presents an epitope to a T-cell receptor. A TMP of the present disclosure is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise a MOD, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a ?2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

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 disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

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 T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides T-cell modulatory multi-merit polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: The present disclosure provides T-cell modulatory polypeptides (TMPs) that comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a ?2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor. A TMP is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: Therapeutic combinations that comprise at least one antagonist of the Programmed Death 1 receptor (PD-1) and at least one benzo[b]thiophene compound that activates the Stimulator of Interferon Genes (STING) pathway are disclosed herein. Also disclosed is the use of such therapeutic combinations for the treatment of cancers.

Abstract: Therapies comprising administering at least one benzo[b]thiophene compound that activates the Stimulator of Interferon Genes (STING) pathway, and the use of such therapies in the treatment of cell-proliferation disorders such as cancer, are disclosed herein.

Abstract: The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide, an epitope-presenting peptide, and class I MHC polypeptides. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

Abstract: Therapeutic combinations that comprise at least one antagonist of the Programmed Death 1 receptor (PD-1) and at least one benzo[b]thiophene compound that activates the Stimulator of Interferon Genes (STING) pathway are disclosed herein. Also disclosed is the use of such therapeutic combinations for the treatment of cancers.

Abstract: Therapies comprising administering at least one benzo[b]thiophene compound that activates the Stimulator of Interferon Genes (STING) pathway, and the use of such therapies in the treatment of cell-proliferation disorders such as cancer, are disclosed herein.

Abstract: Therapies comprising administering at least one cyclic dinucleotide compound that activates the Stimulator of Interferon Genes (STING) pathway, and the use of such therapies in the treatment of cell-proliferation disorders such as cancer, are disclosed herein.

Abstract: Therapeutic combinations that comprise at least one antagonist of the Programmed Death 1 receptor (PD-1) and at least one cyclic dinucleotide compound that activates the Stimulator of Interferon Genes (STING) pathway are disclosed herein. Also disclosed is the use of such therapeutic combinations for the treatment of cancers.