A multi-specific antibody contains at least one binding site for a cell specific antigen and at least one binding site for a tumor-reactive lymphocyte antigen and a multi-specific antibody including an IgG antibody or fragment thereof that binds to a first antigen; and at least one scFv antibody that binds to a second antigen that is different from the first antigen and is linked to a C terminus of at least one light chain or heavy chain of said IgG antibody or fragment. The multi-specific antibody reversibly binds to at least one of the cell specific antigen and tumor-reactive lymphocyte antigen or the first antigen and the second antigen with a greater affinity at an aberrant condition than at a normal physiological condition. Conjugates of the multi-specific antibodies and methods for generating the multi-specific antibody are also provided.

The present invention provides a method to identify and use compounds for the inhibition of abnormal or dysregulated hepatic glucose production that results in elevated blood glucose levels and associated metabolic disorders. The invention is based on the surprising discovery that the glucagon forms an obligate binding complex with aP2, which is necessary for activation of the glucagon G-coupled protein receptor.

Methods are provided for identifying and selecting antibodies that are internalized into cells via the macropinocytosis pathway. Additionally antibodies that are internalized via this pathway are provided as well as immunoconjugates comprising such antibodies.

The present invention relates to soluble multi-domain binding molecules comprising T cell receptors (TCR) having specificity for an antigen, an immunoglobulin Fc domain or an albumin-binding moiety; and an immune effector domain. Such multi-domain binding molecules are advantageous because they display improved half-life while retaining function.

Methods of treating metabolic diseases and disorders using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the antigen binding protein is administered in combination with a GLP-1 receptor agonist.

Provided herein are polypeptides, compositions, and methods for treating a cancer in an individual using a polypeptide comprising a thrombopoietin domain and a Flt3 ligand domain. Also provided herein are nucleic acids encoding such polypeptides, expression vectors and cells comprising such nucleic acids, and methods of producing the polypeptides comprising a thrombopoietin domain and a Flt3 ligand domain. The administration of a fusion polypeptide comprising a thrombopoietin domain and a Flt3 ligand domain to a subject may treat and reduce the symptoms of hematopoietic failure, including thrombopenia, and/or acute radiation syndrome.

Multispecific antibody having a binding site for ICOS and a binding site for a second antigen, e.g., an immune checkpoint molecule such as PD-L1. Use of the multispecific antibody in immuno-oncology, including for treatment of solid tumours.

The present invention discloses an monoclonal antibody, which can bind to HyIL-6 with the binding constant 2.8610.sup.10 and significantly inhibit IL-6/IL-6R/gp130 complex formation. In addition, the monoclonal antibody of the present invention effectively inhibits HyIL-6-stimulated signal transducer and activator of transcription 3 (STAT3) activation and related vascular endothelial growth factor (VEGF) induction. Data from hydrogen deuterium exchange mass spectrometry (HDX-MS) demonstrate that the antibody of the present invention mainly binds to site IIIa of IL-6 and blocks the final step in the interaction between gp130 and IL-6/IL-6R complex. Additionally, data from ELISA binding assays and kinetics assays indicate that the antibody of the present invention interacts simultaneously with IL-6 and IL-6R, while it does not interact with IL-6R alone. The unique features of the antibody of the present invention offer a novel alternative for IL-6 blockade and illuminate a better therapeutic intervention targeting IL-6.

The present invention relates to a conjugate or a fusion protein comprising: (a) an anti-TLT-1 (triggering receptors expressed on myeloid cells like transcript-1) antibody, and (b) a payload, wherein the anti-TLT-1 antibody and the payload are covalently linked together, and the payload is an anti-neoplastic molecule, an anti-mitotic molecule, a transcription or translation inhibitor, or a cytokine. The anti-TLT-1 antibody directs and targets the conjugate or the fusion protein to activated platelets in a tumor microenvironment (TME) through binding of the antibody to TLT-1, a membrane protein receptor that is only present on activated platelets. As a result, the targeted cytotoxic molecules or therapeutic proteins effectively inhibit the tumor growth. The present invention also relates to specific single domain antibodies (sdAbs) or sdAb based heavy chain-only antibody (HcAb) against TREM (triggering receptors expressed on myeloid cells) like transcript-1 (TLT-1).

Antibodies that modulate insulin receptor signaling are provided.