An EL-15 super agonist (IL-15N72D:IL-15RαSU/IgG1Fc; N-803) increases circulating NK cells, effector memory and effector memory RA cells in post-allogeneic hematopoietic stem cell transplant patients (HCT). Methods of treatment include administration of N-803 to subjects in need of such treatment.

The present invention relates to a composition for preventing or treating cancer, the composition containing IL-2 surface expression-extracellular vesicles as an active ingredient. According to the present invention, immune cells, in which useful cytokines have been expressed on the cell surface, and extracellular vesicles, preferably small extracellular vesicles (sEV), which are derived from the immune cells and have useful cytokines expressed on the surface were prepared using a lentiviral vector containing a cytokine-linker-a PDGF receptor transmembrane domain, and it was found that the extracellular vesicles increased proliferation and activity of cytotoxic T cells thereby increasing anti-cancer immune efficacy. Thus, the extracellular vesicles having the efficacy can be usefully utilized as a pharmaceutical composition for preventing or treating cancer, a pharmaceutical composition for co-administration with an anticancer drug, or a composition for delivering a drug or a physiologically active material.

The disclosure relates to methods for treating cancer. More particularly, the disclosure relates to use of chimeric non-natural synthetic proteins, in combination with non-tyrosine targeting kinase inhibitors (NTKIs), in treating cancer and preventing intrinsic and/or acquired resistance to NTKIs.

Provided are activatable proprotein homodimers, comprising at least two separate polypeptide chains, each chain comprising an IL-2 protein variant that has reduced binding affinity to wild-type IL-2Rα relative to that of the wild-type IL-2 sequence, a cleavable linker, and an IL-2 binding protein, among other optional features, and related pharmaceutical compositions and methods of use thereof.

Neurotrophin receptor binding conjugate compositions for delivering an active agent to nerve cells are provided. Conjugate compositions of the present disclosure according to certain embodiments include a one or more active agent compounds (e.g., a dye or small molecule therapeutic) covalently bonded to a protein, peptide or peptidomimetic that binds selectively to a neurotrophin receptor. In embodiments of the compositions, the average ratio of active agent compound to protein, peptide or peptidomimetic in the conjugates is 5 or less. Dual color imaging compositions are also described. Methods for delivering an active agent conjugate selectively into nerve cells (e.g., intraocular delivery) are provided. Also included are methods of making compositions having neurotrophin receptor binding conjugates

Contemplated compositions and methods generate a durable immune synapse and so lead to activated T-cells and memory T-cell formation by use of selected co-stimulatory receptors and their ligands in conjunction with selected neoepitopes. Moreover, immune competent cells are attracted into a tumor microenvironment after activation of the T-cells using hybrid or chimeric binding proteins that comprise a chemokine portion and that target components of necrotic cells.

Provided are methods for treating graft versus host disease (GvHD) by administering a composition an agent comprising an IL-22 (such as an IL-22 dimer), and optionally an immunosuppressive therapy. The treatment can be administered for multiple cycles which are separated by a rest period and/or individuals who have a specific Ann Arbor score or a characterized gut microbiota profile. Also provided are methods of identifying or selecting individuals suitable for such treatments.

The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present invention relates to proteins suitable for being used as scaffolds to which a peptide of interest is bound, or which are comprised within a conjugate to which an agent of interest is attached. It also relates to said conjugates suitable for the selective delivery of their conjugated agents of interest to specific cell and tissue types, wherein said agent 5 can be a therapeutic agent or an imaging agent. It also relates to nanoparticles comprising such conjugates and the therapeutic uses thereof.

Provided are activatable proprotein homodimers, comprising at least two separate polypeptide chains, each chain comprising an IL-2 protein a cleavable linker, and an IL-2 binding protein, among other optional features, and related pharmaceutical compositions and methods of use thereof.