The present disclosure pertains to immune cells comprising exogenous fibrolytic agents and/or exogenous anti-inflammatory agents and methods of using immune cells comprising exogenous fibrolytic agents and/or exogenous anti-inflammatory agents.

Methods and pharmaceutical compositions for treating ischemic injury are provided. The methods include administering a therapeutically effective amount of a vascular matrix metalloproteinase 9 (MMP-9) inhibitor that reduces ischemic injury in a subject.

Proteases regulate a wide range of normal cellular functions where dysregulated activity is observed in various diseases. Compositions and methods use protease activity multiplexed bead-based immunoassays to profile protease activity. This platform technology integrates protease activity measurements with total protein quantification techniques. It represents a significant improvement over existing detection techniques by allowing for multiplexed, sensitive active protease measurements in complex biological samples. Exemplary multiplexed detections are realized in a single assay using a minute sample amount (e.g., 5 μl) for active recombinant MMP-1, -2, -3, -7, 9, and 12 and those same MMPs in cell culture supernatant, menstrual fluid effluent, and peritoneal aspirates. This multiplexed platform achieves high level of sensitivities equal to or better than existing leading single-plex detection strategies. It also allows for high throughput screening to identify inhibitors of proteases in complex, donor-derived samples.

Described herein are targeted ChABC fusion proteins, complexes thereof, and uses thereof. The targeted ChABC fusion proteins can include a ChABC polypeptide that can be linked to a Gal-3 polypeptide. Monomer targeted ChABC fusion proteins can form homogeneous or heterogeneous complexes. The targeted ChABC fusion proteins and complexes thereof can be formulated as pharmaceutical formulations. The targeted ChABC fusion proteins, complexes thereof, and formulations thereof can be administered to a subject in need thereof.

In alternative embodiments, provided are compositions, including pharmaceutical compositions and formulations, products of manufacture and kits, and methods, for: enhancing or accelerating liver regeneration, optionally enhancing or accelerating liver regeneration after tissue injury or liver resection; enhancing or accelerating tissue repair, optionally enhancing or accelerating tissue repair after a trauma, an injury or an infection, wherein optionally the injury is an ischemia-reperfusion injury comprising: administering to an individual in need thereof, a compound or composition capable of inhibiting or decreasing the expression or activity of a matrix metalloproteinase (MMP) in a tissue-specific or tissue-selective manner, in in an end organ specific manner, or administering to the organ, for example, a liver, of an individual in need thereof a compound or composition capable of inhibiting or decreasing the expression or activity of a matrix metallo-proteinase.

Methods of inhibiting MMP-9 are provided. The methods of inhibiting MMP-9 include methods of inhibiting IL-6/TNF-α crosstalk mediated expression and/or secretion of MMP-9. The inhibition of the IL-6/TNF-α crosstalk pathway may be accomplished using an IL-6 signaling inhibitor, such as AG490 or SC-144. The methods may also include the treatment of dieses through the inhibition of IL-6/TNF-α crosstalk mediated production of MMP-9. In an embodiment the methods may include preventing the progression of cancer or cardiovascular disease through the inhibition of the IL-6/TNF-α crosstalk pathway.

Provided herein are IL-15 cytokine prodrugs and methods of making and using thereof.

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

Described herein are oncolytic viruses comprising one or more nucleic acids encoding an engager molecule. In some embodiments, the oncolytic viruses comprise one or more nucleic acids encoding an engager molecule and one or more therapeutic molecules. Pharmaceutical compositions containing the oncolytic virus and methods of treating cancer using the oncolytic viruses are further provided herein.

The invention relates to the field of therapy, in particular dermatology. Inventors herein identify for the first time inhibitors of matrix metalloproteinase-9 (MMP9) as active molecules for use for preventing, treating or alleviating skin depigmenting disorders in a subject in need thereof, and describe compositions and kits comprising such inhibitors as well as uses thereof. Inventors further describe a method for screening pharmaceutically active molecules suitable for preventing, treating or alleviating a depigmenting disorder as well as methods for evaluating the efficacy of a depigmenting disorder treatment involving an inhibitor of MMP9 or for monitoring the course of depigmenting disorder in a subject exposed to such a treatment.