Using protein structural probes one can identify tumor-induced or -produced (TIPS) factors that bind to therapeutic antibodies and change their dynamic structure, thereby negatively affecting their humoral immune functions as well as their pharmacologic activity. Using such protein structural probes and TIPS factors one can screen and identify inhibitors that can counter the binding of TIPS factors to affected therapeutic antibodies. These inhibitors can be used in the presence of a TIPS factor-susceptible antibody (TSA) for treating cancer. An inhibitor can be used alone or in combination with chemotherapy for treating cancer. Patients can be screened to identify those with low or no TIPS factor production as candidates for antibody therapy even in the case in which the antibody is a TSA. Conversely, those with high TIPS factor production are candidates for inhibitor therapy.

In an embodiment, the present disclosure pertains to a method of treating or preventing C. difficile infections. In some embodiments, the method includes administering an anti-toxin to a subject in need thereof. In some embodiments, the anti-toxin includes a designed ankyrin repeat protein (DARPin). In an additional embodiments, the present disclosure pertains to a composition including an anti-toxin for treating or preventing C. difficile infections. In some embodiments, the anti-toxin includes a DARPin. In some embodiments, the anti-toxin is a monomeric or dimeric DARPin for the neutralization of Clostridium difficile toxin B (TcdB).

An artificial immune complex (IC) free in solution, the artificial IC comprising a nucleic acid (NA) folding comprising stapled NA strands, the NA folding having an outer surface patterned with addressable sites and epitopes bound to the addressable sites and displayed in three dimensions for recruiting antibodies free in solution.

The present invention relates to an antibody or a fragment thereof comprising at least one heterologous amino acid sequence incorporated within at least one CDR region of said antibody or fragment thereof, wherein said at least one heterologous amino acid sequence comprises an N-terminal linker sequence (Nils), an Atrial Natriuretic Peptide (ANP) and a C-terminal linker sequence (Ctls). Optionally, at least a portion of said at least one CDR region is replaced by said at least one heterologous amino acid sequence incorporated therein. The present invention further relates to such antibody or fragment thereof for use in a method for treatment, a composition comprising such antibody or fragment thereof, a nucleic acid or a mixture of nucleic acids encoding such antibody or fragment thereof, a host cell comprising such nucleic acid or such mixture of nucleic acids and to a process for producing such antibody or fragment thereof.

Provided are unique affibodies specific for bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), inteleukin-4 (IL-4), and glial derived neurotrophic factor (GDNF), and well as hydrogels that include the affibodies and the corresponding protein. Also provided are methods of using the hydrogels, for example to treat bone injury, wounds, and neuron injury. In some examples, the hydrogel includes at least two different affibodies specific for the same protein, but have different disassociation constants (K.sub.D). Also provided are methods of using the affibodies to treat a disease, wound, injury, or cancer.

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here the inventors show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and 1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions. Accordingly, CD9 represents a reliable biomarker and as well as a biotargets in glomerulonephritides.

The disclosure relates to novel regimens for treating an inflammatory arthiritis. e.g., psoriatic arthritis. which employ a therapeutically effective amount of an Interleukin- 17 (IL-17) antagonist. e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof. e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof).

Provided are dual-affinity fusion proteins including an affibody domain specific for a therapeutic protein, and including a localization domain specific for a structural bone component. The therapeutic protein can include bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), or glial derived neurotrophic factor (GDNF). Also provided are compositions that include the dual-affinity fusion proteins, affibodies and the corresponding therapeutic proteins, and/or a medical material used to treat a wound, or a bone or cartilage injury or disease. Also provided are methods of using the compositions, for example to treat bone injuries, bone diseases, cartilage injuries, cartilage diseases, and wounds. In some examples, the composition includes at least two different dual-affinity fusion proteins specific for the same therapeutic protein, but have different disassociation constants (K.sub.D).

This invention concerns anti-inflammatory agents, compositions, and methods for treating inflammatory disorders.

Disclosed herein are designed ankyrin repeat domain specifically binding to fibroblast activation protein (FAP). Such designed ankyrin repeat domains can be used in recombinant adapter molecules that are displayed on adenoviruses. Adenoviruses armed with such adapters efficiently transduce human fibroblasts and significantly broaden treatment opportunities through paracrine delivery of cargo to the tumor microenvironment (TME).