The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

Provided herein are combinations of an IL-2 molecule or mutein and a TNFR agonist, and complexes comprising IL-2/TNFR agonist molecules, such as Fc-bound IL-2/TNFR agonist molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

Methods and composition for cell-based therapy as well as somatostatin receptor-based therapy are described. For example, in certain aspects methods for administering an anti-tumor therapy using a signaling defective somatostatin receptor mutant are described. Furthermore, the invention provides compositions and methods involve a somatostatin constitutively active somatostatin receptor mutant.

Disclosed herein are ACE2-Fc fusion polypeptides that contain at least one binding site for a spike protein of a coronavirus and methods of using such for therapeutic and/or diagnostic purposes. Also provided herein are methods for producing such fusion polypeptides.

The present disclosure relates to conjugates for delivering therapeutics across the blood brain barrier (BBB) and more particularly to conjugates comprising at least one BBB-shuttling VNAR domain operably linked to a neurotrophic agonist antibody (NAAb), with the conjugate being capable of uptake across a mammalian blood brain barrier (BBB) in a therapeutically-effective amount. These conjugates are useful for treating neurodegenerative diseases, conditions which responds to activation of a neurotrophin receptor as well as for stimulating neuronal survival, growth, repair or regeneration.

Provided are activatable proprotein heterodimers comprising at least two separate polypeptide chains, one chain comprising an IL-2 protein fused to an IL-15 binding protein such as IL-15Rα, and another chain comprising an IL-15 protein fused to an IL-2 binding protein such as IL-2Rα, among other features including binding moieties and cleavable linkers, and related pharmaceutical compositions and methods of use thereof.

Provided are activatable proprotein or procytokine homodimers composed of at least two separate polypeptide chains, each chain comprising a binding moiety such as an Fc region, a cytokine, a cytokine receptor, and at least one a cleavable linker, among other optional features, and related pharmaceutical compositions and methods of use thereof.

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.

Methods and composition for cell-based therapy as well as somatostatin receptor-based therapy are described. For example, in certain aspects methods for administering an anti-tumor therapy using a signaling defective somatostatin receptor mutant are described. Furthermore, the invention provides compositions and methods involve a somatostatin constitutively active somatostatin receptor mutant.

Provided herein are tumor-antigen VGLL 1 specific T cell receptors. The TCR may be utilized in various therapies, such as autologous cell transplantation, to treat a cancer. Methods for expanding a population of T cells that target VGLL 1 are also provided.