Disclosed are a fusion protein comprising a thyrotropin receptor (TSHR) fragment and the use thereof. More specifically, disclosed are a fusion protein comprising a TSHR fragment comprising an extracellular domain of a wild-type TSHR and having a substitution of an amino acid at specific position and an immunoglobulin Fc region or a carboxy-terminal cap (C-CAP), and the use thereof. The fusion protein has improved pharmaceutical efficacy, in-vivo persistence and protein stability and a pharmaceutical composition containing the fusion protein as an active ingredient is useful as a therapeutic agent or diagnostic reagent for the alleviation of Graves' disease and Graves' ophthalmopathy.

Disclosed are a fusion protein comprising a thyrotropin receptor (TSHR) fragment and the use thereof. More specifically, disclosed are a fusion protein comprising a TSHR fragment comprising an extracellular domain of a wild-type TSHR and having a substitution of an amino acid at specific position and an immunoglobulin Fc region or a carboxy-terminal cap (C-CAP), and the use thereof. The fusion protein has improved pharmaceutical efficacy, in-vivo persistence and protein stability and a pharmaceutical composition containing the fusion protein as an active ingredient is useful as a therapeutic agent or diagnostic reagent for the alleviation of Graves' disease and Graves' ophthalmopathy.

The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the V.sub.H, V.sub.L, and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the invention contemplate using anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, photophobia, mast cell degranulation, and/or neuronal activation, would be therapeutically beneficial.

The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the V.sub.H, V.sub.L, and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the invention contemplate using anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, photophobia, mast cell degranulation, and/or neuronal activation, would be therapeutically beneficial.

The present invention is directed to transduced T cells expressing at least 100,000 molecules of human somatostatin receptor 2 (SSTR2), which improves PET/CT imaging sensitivity. The present invention is also directed to transduced T cells expressing SSTR2 and chimeric antigen receptor (CAR). In one embodiment, the CAR is specific to human ICAM-1 and the CAR comprises a binding domain that is scFv of anti-human ICAM-1, or an I domain of the αL subunit of human lymphocyte function-associated antigen-1. In another embodiment, the CAR is specific to human CD19, and the CAR comprises a binding domain that is scFv of anti-human CD19. The present invention is further directed to using the above transduced T cells for monitoring T cell distribution in a patient by PET/CT imaging and/or treating cancer.

This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

Described herein are microbial probiotics that, in response to metabolite extracellular ATP (eATP) produced in the microenvironment of inflamed tissues detected, e.g., via an engineered mammalian P2Y2 receptor, secrete an anti-inflammatory protein, e.g., IL-2, IL-10, or the CD39-like eATP-degrading enzyme apyrase. Thus, provided herein is an isolated Saccharomyces cell (or cells, e.g., a population of such cells) that has been engineered to express one, two, or all three exogenous proteins selected from: (I) a mammalian P2Y purinoceptor 2 (P2Y2) protein, preferably human P2Y2; 15 (ii) a mutant Gpa1 protein comprising at least 5 C-terminal residues from a mammalian G alpha, preferably Gai3, wherein the mutant Gpa1 protein couples the P2Y2 protein to the yeast mating pathway; and (iii) an anti-inflammatory protein.

Disclosed are nucleic acid vectors comprising a CBh promoter operably linked to a heterologous sequence encoding a G-protein coupled receptor (GPCR). In some embodiments, composition further comprise a sequence encoding an affinity tag, optionally comprising a SNAP polypeptide. In some embodiments, the GPCR comprises a metabotropic glutamate receptor (mGluR), which is optionally, mGluR2. The disclosure also provides compositions and genetically modified cells comprising these vectors. Methods of treatment of retinal diseases and disorders comprising administering compositions, vectors, and cells of the disclosure to a subject in need are also provided.

A trigger-responsive immune-inactivating signaling polypeptide disclosed herein can include a modulating domain and an immune-inactivating moiety, such as a dominant negative signaling moiety or constitutively active signaling moiety. A modulating domain can be characterized by an ability to adopt a first state and a second state, and to transition between the first state and the second state when exposed to a trigger. When the modulating domain is in its first state, the immune-inactivating signaling moiety can be inhibited, and when the modulating domain is in its second state, the inhibition can be relieved. Further disclosed herein are compositions for the delivery of a trigger-responsive immune-inactivating signaling polypeptide. Also, methods for using a trigger-responsive immune-inactivating signaling polypeptide, including to regulate an activity of immune system cells, are disclosed.