The present disclosure provides a population of poly-donor CD4.sup.IL-10 cells generated by genetically modifying CD4.sup.+ T cells from at least three different T cell donors. Further provided are methods of generating the poly-donor CD4.sup.IL-10 cells and methods of using the poly-donor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and other immune disorders.

Provided herein are anti-FN-EIIIB nanobodies, conjugates thereof, and methods of using the nanobodies and conjugates thereof.

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

The present invention provides methods for targeting interleukin-10 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using an interleukin-10 (IL-10) variant conjugated to a biologically active molecule that will affect cells expressing the interleukin-10 receptor.

Tumor infiltrating lymphocytes (TILs) are white blood cells that are actively recruited to the tumor site to mount an immune response against tumor growth and metastasis. The disclosure provides methods for treating cancer that comprise steps of isolating CD8+ T cells from a sample derived from a subject, expanding the CD8+ T cells in the presence of interleukin-10, and ad ministering the expanded CD8+ T cells to the subject. Methods of treating cancer may be used in combination with inhibitors of the complement signaling pathway.

A nucleic acid molecule comprising a nucleotide sequence encoding a homodimeric IL-10 linked to a transmembrane-intracellular stretch, optionally through a flexible hinge, is provided as well as a mammalian regulatory T cell (Treg) comprising and expressing the nucleic acid molecule and uses thereof.

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.

Provided herein are systems, compositions, and methods for expressing an antigen and a protein having interleukin-10-like activity in a cell. The systems, compositions, and methods described herein can be used to induce an immune response against an antigen and are useful, for example, in the prevention and treatment of a number of infectious diseases and cancers.

Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the Lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.