This invention relates to novel hetero-dimeric multi-specific format of multiple antibody variable domains comprising a core of two split variable domain pairs wherein both variable light domains and the two cognate variable heavy domains are positioned in tandem on two separate protein chains, respectively.

The present disclosure relates to a pair of flanking sequences for a split intein wherein, the pair of flanking sequences comprises: a flanking sequence a and a flanking sequence b; the flanking sequence a is located at the N-terminus of the split intein N-terminal protein splicing region (In), and is between the N-terminal extein (En) and the In; the flanking sequence b is located at the C-terminus of the split intein C-terminal protein splicing region (Ic), and is between the Ic and the C-terminal extein (Ec); and the split intein is NpuDnaE.

The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.

The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

The present invention provides antibodies that specifically bind to FLT3 (Fms-Like Tyrosine Kinase 3). The invention further provides bispecific antibodies that bind to FLT3 and another antigen (e.g., CD3). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific). The invention further relates to therapeutic methods for use of these antibodies for the treatment of FLT3-mediated pathologies, including cancer such as Acute Myeloid Leukemia (AML).

Disclosed herein are methods of treating a subject exhibiting a cell that expresses Wilms tumor protein 1 (WT1). The methods typically utilize anti-WT1 antigen binding units or chimeric antigen receptor immunoresponsive cells to a subject in need thereof to effect killing of tumor cells.

An object of the present invention is to provide a bacterium of the genus Bifidobacterium exerting an anti-tumor effect against solid cancers sustainably and specifically. Produced is a bacterium of the genus Bifidobacterium expressing a first polypeptide comprising a light-chain variable region (VL) that binds to human CD3 and a heavy-chain variable region (VH) that binds to a human tumor cell surface antigen; and a second polypeptide comprising VL that binds to a human tumor cell surface antigen and VH that binds to human CD3 and secreting a diabody-type bispecific antibody composed of the first polypeptide and the second polypeptide.

The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

Provided are molecular constructs that target tumor necrosis factor receptor 1 (TNFR1) and/or tumor necrosis factor receptor 2 (TNFR2). The constructs are for treating diseases, disorders, and conditions in which these receptors and/or TNF are involved in the etiology or in which their inhibition or activation thereof can ameliorate the disease, disorder, and condition or a symptom thereof. Among the constructs provided herein, are TNFR1 antagonist constructs that are engineered to inhibit TNFR1 function, and to eliminate any TNFR1 agonist activity. The constructs provided herein include agonists and antagonists of TNFR1 and TNFR2 Included also are agonists and antagonists of TNFR2. Agonists of TNFR2 increase regulatory T-cell function to control acute or chronic inflammation. Antagonists of TNFR2 decrease regulatory T-cell function thus increasing immunity, and are for treating cancer and certain immunodeficiency diseases. Methods of treatment of the various diseases in which TNF and its receptors play a role also are provided. Also provided are growth factor ligand trap constructs, and methods of use thereof for treatment of diseases, disorders, and conditions, including cancer.