Abstract: The present disclosure provides a method for the treatment of neoplastic disease in a mammalian subject the method comprising the administration of an IL-10 agent in combination with the administration of at least one modulator of at least one immune checkpoint pathway. The present disclosure further provides a method for the treatment of neoplastic disease wherein the neoplasm has a low or intermediate tumor mutation burden, low or intermediate level of expression of the immune checkpoint molecule, or metastatic neoplastic disease.

Abstract: The present disclosure relates to hIL2 orthogonal ligands (“IL2 orthologs”) that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.

Abstract: Human lymphocytes or myeloid cells comprising a polynucleotide encoding an engineered orthogonal human CD122, wherein the lymphocyte or myeloid does express native human CD122 are provided.

Abstract: The present disclosure provides methods and compositions relating to isolated CD8+ T cells expressing a disease antigen-specific T cell receptor, as well as nucleic acids encoding the V? and V? polypeptide pairs of T cell receptors (TCRs) of such disease antigen-specific T cells. Such disease antigen-specific CD8+ T cells are obtainable from the periphery (e.g., blood) of a subject having a disease amenable to treatment with an IL-10 agent. The present disclosure also contemplates therapeutic methods and compositions relating to administration of isolated disease antigen-specific CD8+ T cells to a subject, as well as therapeutic methods and compositions relating to CD8+ T cells genetically modified to express a disease antigen-specific TCR and/or chimeric antigen receptor.

Abstract: The present disclosure is directed to a recombinantly modified immune cell comprising a nucleic acid sequence encoding a receptor comprising an orthogonal extracellular domain and a nucleic acid sequence encoding an orthogonal ligand that exhibits specific binding for the orthogonal extracellular domain of the receptor.

Abstract: The present disclosure relates to hIL2 orthogonal ligands (“IL2 orthologs”) that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.

Abstract: The present disclosure provides orthogonal receptors. In some embodiments, the orthogonal receptor is an orthogonal CD122. In some embodiments, the orthogonal receptor is an orthogonal human CD122 (hCD122). In some embodiments, the orthogonal receptor is an orthogonal CD122 comprising at least one STAT3 binding motifs.

Abstract: The present disclosures related to human interleukin-2 (hIL2) muteins, pharmaceutical formulations thereof, methods for preparing interleukin-2 muteins, recombinant vectors and cells comprising nucleic acids encoding IL2 muteins and methods for the treatment of human disease.

Abstract: The present disclosures related to human interleukin-2 (hIL2) muteins, pharmaceutical formulations thereof, methods for preparing interleukin-2 muteins, recombinant vectors and cells comprising nucleic acids encoding IL2 muteins and methods for the treatment of human disease.

Abstract: Methods of treating subjects having diseases, disorders, or conditions, including cancer and immune- and inflammatory-related disorders, via the administration of IL-10 in combination with one or more additional agents, and methods and models associated therewith, are provided.

Abstract: The present invention relates to methods of modulating the activity of CAR-T cells in the treatment of diseases, disorders and conditions by the administration of an IL-10 agent. The invention further provides engineered CAR-T cells to express additional therapeutically effective agents. The present invention further provides improved pharmaceutical and therapeutic compostions and methods relating to the use of CAR-T cell therapies in the treatment of disease in mammalian subjects.

Abstract: The present disclosures related to human interleukin-2 (hIL2) muteins, pharmaceutical formulations thereof, methods for preparing interleukin-2 muteins, recombinant vectors and cells comprising nucleic acids encoding IL2 muteins and methods for the treatment of human disease.

Abstract: The present disclosure relates to hIL2 orthogonal ligands (“IL2 orthologs”) that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.

Abstract: The present disclosure provides a method for the treatment of neoplastic disease in a mammalian subject the method comprising the administration of an IL-10 agent in combination with the administration of at least one modulator of at least one immune checkpoint pathway. The present disclosure further provides a method for the treatment of neoplastic disease wherein the neoplasm has a low or intermediate tumor mutation burden, low or intermediate level of expression of the immune checkpoint molecule, or metastatic neoplastic disease.

Abstract: Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.

Abstract: Provided are methods of treatment for tumors. In particular, methods are provided for use of a chemically modified IL-10 to treat tumors.

Abstract: Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.

Abstract: Methods of treating subjects having a cancer-related, immune-related, or viral-related disease, disorder or condition via administration of an IL-10 agent, including pegylated IL-10, and an IL-7 agent are provided, as are methods of identifying subjects that may be responsive to treatment with an IL-10 agent.

Abstract: Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.

Abstract: Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.