This document provides methods and materials involved in treating chronic liver disease (e.g., non-alcoholic fatty liver disease such as nonalcoholic steatohepatitis (NASH)). For example, methods and materials for using one or more inhibitors of an integrin β1 (ITGβ1) polypeptide, one or more inhibitors of an integrin α9 polypeptide (ITGα9), and/or one or more inhibitors of a vascular cell adhesion molecule 1 (VCAM-1) polypeptide to treat a mammal having chronic liver disease are provided.

The present disclosure provides activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM). The present disclosure provides activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM. Furthermore the present disclosure also provides ABPs which contain a first TBM, a second TBM and a CM. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. The disclosure further provides libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. The disclosure further provides ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

Herein is reported a method for increasing the (avid-)binding specificity of a bispecific antibody comprising a first mammalian or mammalianized binding site specifically binding to a first (cell-surface) antigen and a second binding site specifically binding to a second (cell-surface) antigen, wherein the first mammalian or mammalianized binding site is at least a pair of an immunoglobulin light chain variable domain and immunoglobulin heavy chain variable domain, by decreasing the binding affinity of the mammalian or mammalianized binding site to its antigen by mutating in the first mammalian or mammalianized binding site at least one amino acid residue at a position in the CDRs of the light chain variable domain or in the CDR1 or CDR2 of the heavy chain variable domain or in the two framework positions directly preceding the CDR3 in the heavy chain variable domain to an amino acid residue present at said position in a germline immunoglobulin amino acid sequence of the same mammalian species as that of the mammalian or mammalianized binding site.

Methods for treating and reducing the progression of neurodegenerative diseases, including, without limitation Alzheimer's disease, are provided. The methods of the invention reduce or deplete neutrophil/myeloid cells in the region of the brain by blocking neutrophil/myeloid cell adhesion and interaction with the vascular endothelium, by blocking infiltration of neutrophil/myeloid cells into the brain, by reducing motility of neutrophil/myeloid cells in the parenchyma, by blocking Aβ-induced activation and adhesion of neutrophil/myeloid cells, and/or by blocking Aβ-induced integrin activation, degranulation and/or ROS release in neutrophil/myeloid cells.

This disclosure relates to compositions and methods for treating cancer using armored chimeric antigen receptor cells.

The invention provides novel targeted particles as contrast agents for use in molecular imaging of vulnerable plaque, and methods of preparation and application thereof.

Compositions comprising a dual-targeted nanoparticle having a first targeting moiety and a second targeting moiety, wherein said first targeting moiety is a red blood cell (RBC)-targeting moiety are provided. In certain embodiment, the nanoparticles are bound to RBCs ex vivo. Also provided are methods of delivering selected drugs to target organs using these compositions for treatment of disease or for diagnostic imaging.

A novel fluorophore based on an acid soluble reagent that is a lanthanide metal ion nanoparticle that is passivated and/or coated for water dispersion and to minimize nonspecific binding, and assays for same

Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an “activatable” conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

Antibodies and antibody fragments that inhibit the activity of vascular cell adhesion molecule 1 (VCAM1) and/or macrophage erythroblast attacher (MAEA) are provided, along with formulations and kits comprising these antibodies and antibody fragments and the use of the disclosed compositions, formulations, and kits to treat cancers, sickle cell disease, and Polycythemia Vera.