In certain embodiments, the present invention provides a musclin peptide and methods of increasing muscle growth, performance, resistance to injury and/or preventing or reducing muscle atrophy and improving overall skeletal muscle, metabolic and cardiac health in an animal in need thereof by administering a musclin peptide.

The present invention provides VEGF mini-trap molecules and method of treating or preventing angiogenic disorders such as angiogenic eye disorders and cancer.

The present invention provides VEGF mini-trap molecules and method of treating or preventing angiogenic disorders such as angiogenic eye disorders and cancer.

The present invention relates to methods and pharmaceutical composition for treating inflammatory diseases. Inflammation is a defence response to tissue damage or infections that requires tight regulation to prevent impaired healing and to avoid excessive damage and/or autoimmunity. Myeloid cells, including macrophages play a key role in tissue repair and undergo major functional changes during the healing processes, switching from an inflammatory state to a pro-repair phenotype. The inventors have found that TAFA4, a chemokine-like protein, has anti-inflammatory and pro-repair properties. This molecule regulates the phenotype of man monocytes and macrophages by promoting their anti-inflammatory and pro-repair functions. TAFA4 increases macrophage their phagocytic capacities and their production of the anti-inflammatory cytokine IL-10. By contrast, TAFA4 down-regulates the production of the pro-inflammatory cytokines IL-6, IL-113, and TNF-α by human macrophages. Importantly, the inventors have also found that a treatment with TAFA4 has anti-inflammatory effects in vivo and protects mice from LPS-induced endotoxic shock. This protective effect is associated with a reduction in inflammatory cytokine levels and an increase in EL-10 production. Finally, they found that TAFA4 can also exert its anti-inflammatory properties on peripheral blood mononuclear cells from COVID-19 patients, independently of the disease severity. Thus, the present invention relates to a TAFA4 polypeptide or a nucleic acid molecule encoding thereof for use in the treatment of inflammatory diseases.

Provided herein are methods for expanding NK cells expressing chimeric antigen receptors and/or T cell receptors. Further provided are methods for treating diseases by administering the CAR NK cells.

Provided are combination therapies and secondary biomarkers for treating MYCC-associated diffuse large B-cell lymphoma (DLBCL) with YM155-based therapies, and related kits, compositions, and methods of use thereof.

Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.

Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants. The present invention also provides a mutant protein which has the same amino acid sequence of a wild type PF4 monomer except that (i) at least one amino acid of the wild type PF4 monomer has been deleted, (ii) at least one amino acid of the wild type PF4 monomer has been replaced by another amino acid, or (iii) a combination of such changes has been made. The present invention also provides methods of treating or reducing the likelihood of HIT, treating angiogenesis, treating abnormal cell growth, or affecting coagulation pathologies that lead to thrombus formation, by administering such mutant proteins to a patient.

Disclosed are conjugates of biomolecule and use thereof. The disclosed conjugates of biomolecule contain a biomolecule and a functional moiety covalently linked to the biomolecule. The functional moiety contains a group that prevents the biomolecule from binding to its ligand or receptor, a cleavable linker arm that can be activated by proteolytic enzymes or can be acidically activated in a microenvironment of a disease, a linker arm that will automatically shed after the cleavable linker arm is cleaved, and a group that maintains or promotes the binding capacity of the biomolecule to its ligand or receptor. The conjugates of biomolecule of the present disclosure can effectively reduce immunogenicity of the biomolecule, increase it's half-life, and break through the immune barrier of an individual, reach a pathologic microenvironment and be activated and released in the pathologic microenvironment, selectively promoting proliferation or killing effect of T cells and the like in the tumor, thereby preventing on target off tumor toxicity or in the inflammatory microenvironment of autoimmune disease and achieving a low autoimmunity and high efficacy.