The present invention relates to compositions and methods for diagnosing and treating diseases, disorders or conditions associated with dysregulated expression of GPC3. The invention provides novel antibodies that specifically bind to glypican-3 (GPC3). The invention also relates to a fully human chimeric antigen receptor (CAR) wherein the CAR is able to target GPC3.

Antibodies or antigen-binding fragments thereof are engineered to bind Transforming Growth Factor-β (TGFβ). TGFβ-isoform selective antibodies or antigen-binding fragments thereof may selectively bind human TGFβ1, compared to human TGFβ2 and human TGFβ3, or may selectively bind human TGFβ3, compared to human TGFβ1 and human TGFβ2. The design of the antibodies or antigen-binding fragments thereof is facilitated by a co-crystal structure of a recombinant Fab fragment of GC1008 bound to TGFβ2 and by another co-crystal structure of the scFv version of GC1008 bound to TGFβ1.

The instant disclosure provides antibodies that specifically bind to CD137 (e.g., human CD137) and increases CD137 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

The present invention pertains to antibodies against a novel isoform of human PD1 protein (Δ42PD1) that contains a 42-nucleotide in-frame deletion in exon 2. The invention also pertains to methods of using the antibodies against Δ42PD1 for the treatment for autoimmune disorders. In certain embodiments, the antibodies against Δ42PD1 are monoclonal.

Disclosed herein are methods and compositions related to single chain antibody fragments which specifically bind sialyl-Tn epitope of tumor-associated glycoprotein 72 (TAG-72).

The present disclosure provides humanized anti-C1s antibodies. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the humanized anti-C1s antibodies; and host cells comprising the nucleic acids. The present disclosure provides compositions comprising the humanized anti-C1s antibodies. The present disclosure provides methods of use of the humanized anti-C1s antibodies.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses a single light chain variable domain derived from a single rearranged light chain variable region gene in the germline of the non-human animal, wherein the single rearranged light chain variable region gene comprises a substitution of at least one non-histidine encoding codon with a histidine encoding codon. Methods of making non-human animals that express antibodies comprising a histidine-containing universal light chain are provided.

An agonistic 4-1BB monoclonal antibody or an antigen binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a CDR1 region having an amino acid sequence as shown in SEQ ID NO: 1, a CDR2 region having an amino acid sequence as shown in SEQ ID NO: 2, and a CDR3 region having an amino acid sequence as shown in SEQ ID NO: 3, the light chain variable region comprising: a CDR1 region having an amino acid sequence as shown in SEQ ID NO: 4, a CDR2 region having an amino acid sequence as shown in SEQ ID NO: 5, and a CDR3 region having an amino acid sequence as shown in SEQ ID NO: 6. The monoclonal antibody is targeted towards h4-1BB, and specifically binds to h4-1BB to activate T cells for treatment of a variety of cancers.

Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.