The present disclosure provides a use of a dimer in the preparation of a medicament for treating a tumor in a subject in need thereof, and the dimer formed by two polypeptide chains, with each of the two polypeptide chains comprising an antibody Fc subunit, wherein the dimer comprises two or more immunoglobulin single variable domains (ISVDs), at least one of the ISVDs is specific for PD-L1, and at least one of the ISVDs is specific for CTLA4. The present disclosure also provides a method for treating a tumor in a subject in need thereof, wherein the subject is resistant to the therapy of an immune checkpoint inhibitor.

The present disclosure provides a use of an immune checkpoint inhibitor in combination with a Her2 inhibitor in the preparation of a medicament for treating tumor in a subject in need thereof, and also provides a pharmaceutical composition comprising an effective amount of said immune checkpoint inhibitor and an effective amount of said Her2 inhibitor, and optionally a pharmaceutically acceptable excipient, as well as a use of the pharmaceutical composition in the preparation of a medicament for treating tumor in a subject in need thereof.

Disclosed herein are multi-specific antibody constructs that simultaneously bind two tumor cell surface antigens, GD2 and B7H3. The monovalent arms targeting GD2 and B7H3 are each low to moderate affinity for their respective antigens. The multi-specific antibodies disclosed herein bind to target tumor cells when both arms of the antibody bind to their antigens, resulting in high specificity of the antibody for GD2 and B7H3 expressing tumor cells.

Herein is reported a method for producing a bispecific antibody comprising the step of incubating (i) an antibody Fab fragment or a scFv antibody comprising within the 20 C-terminal amino acid residues the amino acid sequence LPX1TG (SEQ ID NO: 01), (ii) a one-armed antibody comprising a full length antibody heavy chain, a full length antibody light chain, and an Fc-heavy chain, whereby the full length antibody heavy chain and the full length antibody light chain are cognate antibody chains that thereof forms an antigen binding site, whereby the full length antibody heavy chain and the Fc-heavy chain are covalently linked to each other via one or more disulfide bonds forming an antibody hinge region, and whereby the Fc-heavy chain has an oligoglycine amino acid sequence at its N-terminus, and (iii) a Sortase A enzyme.

The present invention provides bispecific antibodies that bind to CD3 and tumor antigens and methods of using the same. According to certain embodiments, the bispecific antibodies of the invention exhibit reduced effector functions and have a unique binding profile with regard to Fcγ receptors. The bispecific antibodies are engineered to efficiently induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, a second antigen-binding molecule that specifically binds human CD20, and an Fc domain that binds Fcγ receptors with a specific binding pattern. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell or melanoma tumors expressing CD20. The bispecific antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

Provided herein are modified T cell engagers, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same. The modified T cell engagers described herein are modified with a peptide and a half-life extending molecule.

Herein are disclosed anti-S100A4 neutralizing antibodies useful for the treatment of the disease systemic sclerosis. The disclosure also provides isolated polynucleotides, vectors, isolated host cells, compositions and pharmaceutical compositions for the treatment of systemic sclerosis.

Compositions and methods for selective targeting of BMP/TGF? signaling using heteromeric complexes, preferably comprising single chain variable domain (scFv) antibodies (Abs) targeting the extracellular domains of BMP type I and type II receptors.

Compositions, e.g., compositions comprising protein therapeutics, and methods of using such compositions for treating cancer are described.