Disclosed are methods of identifying immunosuppressive T.sub.R1 regulatory T cells, including methods of diagnosing the presence of immune tolerance, methods of producing immunosuppressive regulatory T cells, and methods of eliciting immune tolerance in a subject. These methods include screening T cells to detect Eomes.sup.+IL-10.sup.+ T cells or expressing recombinant Eomes in T cell populations to generate immunosuppressive regulatory T cells.

Recombinant oncolytic viruses (OVs) that express one or more metabolic modulator proteins, such as an adipokine (e.g., leptin or chemerin), insulin, and/or IGF-1, and methods of their use to treat cancer, for example in immunotherapy anti-cancer treatments. In some examples, such recombinant OVs and methods increase T cell infiltration into the tumor or tumor microenvironment.

The present disclosure pertains to immune cells comprising exogenous fibrolytic agents and/or exogenous anti-inflammatory agents and methods of using immune cells comprising exogenous fibrolytic agents and/or exogenous anti-inflammatory agents.

Disclosed herein are interleukin 10 conjugates and uses in the treatment of one or more indications. Also described herein are pharmaceutical compositions and kits comprising one or more of the IL-10 conjugates.

The present disclosure provides antibodies, including antibody fusions, which specifically bind to human PD-L1 protein (huPD-L1) and are capable of decreasing, inhibiting, and/or fully-blocking immune regulatory effects mediated by PD-L1, such as binding to the immune checkpoint molecule PD-1 in the tumor microenvironment. Additionally, the antibodies include fusions with the cytokine inhibitory factor, IL10, which can replenish and/or activate CD8+ T-cell cytotoxicity in the tumor microenvironment. The present disclosure also provides methods of using the antibodies (and compositions thereof) to treat diseases and conditions responsive to decreasing, inhibiting and/or blocking immune regulatory function or activity mediated by PD1 binding to PD-L1.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising the alpha and beta multi-subunits cytokines, such as IL-12 or IL-27, fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

The present disclosure relates to IL10 agonists with improved anti-tumor therapeutic efficacy.

Abstract: The present disclosure is directed to fusion proteins comprising a Tumor Necrosis Factor α (TNFα) binding protein and an interleukin-10 (IL-10) molecule, methods of making the fusion proteins, and methods of treating or preventing autoimmune and inflammatory conditions using the fusion proteins.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.