In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

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.

A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13Rα2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.

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 invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

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 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.

The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.