A therapeutic molecule (single chain-based antibody or ligand-based) optimized for expression and secretion from engineered T cells, which may be gamma delta (gd) T cells. When expressed from engineered gdT cells, the STAR will be secreted and mediate engagement between gdT cells and antigen/receptor on target cells. Binding mediates the formation of a cytolytic synapse between the gdT cell and the target cell leading to activation the gdT cells to release proteolytic enzymes that kill target cells.

The present invention relates to a pharmaceutical composition for inhibiting the resistance of liver cancer to sorafenib and enhancing an anticancer effect, comprising an Estrogen-related receptor γ (ERRγ) inhibitor as an active ingredient. The present invention can be effectively used as a pharmaceutical composition for treating sorafenib-resistant advanced liver cancer.

This application provides isolated antibodies, and antigen-binding fragments thereof, that specifically bind endothelin A receptor (ET.sub.AR). These ET.sub.AR antibodies, or antigen-binding fragments thereof, have a high affinity for ET.sub.AR, function to effectively block ET-1 binding to ET.sub.AR, are less immunogenic compared to their unmodified parent antibodies in a given species (e.g., in a human), and can be used to treat ET.sub.AR-associated disorders. Importantly, compared to small molecule ET.sub.AR antagonists, the antibodies of the present invention have advantages of longer serum half-life, higher target specificity, thereby limiting the risk of off-target toxicity and improving therapeutic window.

Provided herein are a glucagon receptor (GCGR) antibody and its fusion protein with glucagon-like peptide-1 (GLP-1), and a pharmaceutical composition thereof. Also provided herein is a method for using the GCGR antibody and its fusion protein with GLP-1 to treat, prevent or improve one or more symptoms of hyperglycemia, type 2 diabetes, metabolic syndrome or dyslipidemia.

Provided herein are a gastric inhibitory polypeptide receptor (GIPR) antibody and its fusion protein with glucagon-like peptide-1 (GLP-1), and a pharmaceutical composition thereof. Also provided herein is a method for using the GIPR antibody and its fusion protein with GLP-1 to treat, prevent or improve one or more symptoms of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, type 2 diabetes or obesity.

The present invention provides antibodies and antigen-binding fragments of antibodies that bind to leptin receptor (LEPR), and methods of using the same. According to certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR and antagonize LEPR signaling. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR in the presence or absence of leptin. In other embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that exhibit partial agonism of LEPR signaling. The antibodies and antigen-binding fragments of the present invention are useful for the treatment of various conditions, including but not limited to congestive heart failure cachexia, pulmonary cachexia and cancer cachexia, autoimmune disorders such as inflammatory bowel disease, lupus erythematosus, multiple sclerosis, psoriasis, cardiovascular diseases, elevated blood pressure, neurodegenerative disorders, depression, cancer such as hepatocellular carcinoma, melanoma, breast cancer, and other diseases and disorders associated with or caused by elevated leptin signaling.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. The CAR may comprise a mutant CD28 costimulatory domain.

Methods of treating diseases and disorders characterized by elevated levels of cortisol using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the disease or disorder is Cushing's syndrome.

The present invention discloses an application of a β3 adrenergic receptor (ADRB3) as a marker for detecting a plurality of diseases, and an application of anti-human ADRB3 monoclonal antibody in diagnosing a disease and preparing a drug for treating the disease. The present invention finds through research that the ADRB3 is a key receptor in nerve-endocrine-immunoregulatory network, and an ADRB3-mediated signaling pathway regulates proliferation and differentiation of neutrophils, lymphocytes and tumor cells. Under normal circumstances, the ADRB3 maintains the non-specific immunocompetence and specific immunocompetence of an organism, and eliminates pathogenic microorganisms and aged organism tissues to play a role in protecting the organism and anti-aging. Under pathological conditions, excessive activation of the signaling pathway will cause systemic chronic inflammation, and destroy immune homeostasis. Therefore, the ADRB3 can be used as a diagnostic marker and a therapeutic target for a plurality of diseases. Anti-human ADRB3 antibody can specifically bond with the ADRB3, regulate the activity of the ADRB3, has the functions of resisting cancer, inflammation, poisoning, shock, allergy, viral infection, autoimmune disease, disease caused by regenerative dysfunction, autoimmune disease, cachexia, cardiovascular and cerebrovascular disease, neurodegenerative disease and aging, regulating autophagy, treating aging disease, etc., and has important medical value and research and application prospects.

The present invention provides novel antibodies that specifically bind to GUCY2c and uses thereof in the treatment of cancer. The present invention further provides novel bispecific antibodies comprising such antibodies and uses thereof in the treatment of cancer.