Abstract: Provided are methods of treating cancer (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), HER2-positive gastric/gastroesophageal junction (GEJ) cancer, de novo or transformed diffuse large B cell lymphoma (DLBCL), or indolent lymphoma) in an individual that comprise administering to the individual (a) a polypeptide comprising a SIRP? D1 domain variant and an Fc domain variant, and (b) an anti-cancer antibody (e.g., an anti-PD1 antibody, anti-HER2 antibody, or an anti-CD20 antibody). Also provided are related kits pharmaceutical compositions.

Abstract: Provided herein, inter alia, are isolated, humanized antibodies that bind an extracellular domain of a human SIRP-? polypeptide. Also provided are polynucleotides, vectors, host cells, and methods of production and use related thereto.

Abstract: The present application provides activatable antibodies comprising an antibody comprising an antigen-binding domain (ABD), wherein the ABD comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the N-terminus of the VH is fused to a first polypeptide shield moiety (S1), and the N-terminus of the VL is fused to a second polypeptide shield moiety (S2), wherein S1 comprises a first disease-sensing releasable moiety (DS1) and/or S2 comprises a second disease-sensing releasable moiety (DS2), wherein association of S1 with S2 blocks binding of the ABD to its target, and wherein the ABD does not specifically bind to S1, S2, or association thereof. Composition, methods of treatment using the activatable antibodies, and methods of preparation thereof are further provided.

Abstract: Provided are methods of treating cancer that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRP? D1 domain variant and an Fc domain variant in combination with at least one chemotherapy agent and/or at least one therapeutic antibody. Also provided are related kits.

Abstract: The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Abstract: Provided are methods of treating cancer (e.g., a urothelial cancer) that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRP?-D1 domain variant and an Fc domain variant in combination with an antibody-drug conjugate (e.g., enfortumab vedotin). Also provided are related kits.

Abstract: Provided herein are antibody-peptide fusion proteins comprising an amyloid-reactive peptide linked to an antibody. Also provided herein are methods of treating amyloid-based diseases by administering an antibody-peptide fusion protein.

Abstract: The invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-a variants. The constructs may be engineered in a variety of ways to respond to environmental factors, such as pH, hypoxia, and/or the presence of tumor-associated enzymes or tumor-associated antigens. The constructs of the invention may be used to treat various diseases, such as cancer, preferably solid tumor or hematological cancer.

Abstract: The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Abstract: Provided are methods of treating cancer that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRP? D1 domain variant and an Fc domain variant in combination with at least one chemotherapy agent and/or at least one therapeutic antibody. Also provided are related kits.

Abstract: The present disclosure features signal-regulatory protein ? (SIRP-?) polypeptides and constructs that are useful, e.g., to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T-cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof. The SIRP-? constructs include a high affinity SIRP-? D1 domain or variant thereof that binds CD47 with higher affinity than a wild-type SIRP-?. The SIRP-? polypeptides or constructs include a SIRP-? D1 variant fused to an Fc domain monomer, a human serum albumin (HSA), an albumin-binding peptide, or a polyethylene glycol (PEG) polymer. Compositions provided herein include (i) a polypeptide including a signal-regulatory protein ? (SIRP-?) D1 variant and (ii) an antibody.

Abstract: The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Abstract: Provided are methods of treating cancer (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), HER2-positive gastric/gastroesophageal junction (GEJ) cancer, de novo or transformed diffuse large B cell lymphoma (DLBCL), or indolent lymphoma) in an individual that comprise administering to the individual (a) a polypeptide comprising a SIRP? D1 domain variant and an Fc domain variant, and (b) an anti-cancer antibody (e.g., an anti-PD1 antibody, anti-HER2 antibody, or an anti-CD20 antibody). Also provided are related kits pharmaceutical compositions.

Abstract: Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-? v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-? v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-? polypeptide, an extracellular domain of a mouse SIRP-? polypeptide, an extracellular domain of a human SIRP-? polypeptide, and/or an extracellular domain of a human SIRP-? polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-? polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-? polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

Abstract: Provided are methods of treating cancer (e.g., a hematological cancer such as myelodysplastic syndrome) that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRP? D1 domain variant and an Fc domain variant in combination with a hypomethylating agent (e.g., azacitidine). Also provided are related kits.

Abstract: The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Abstract: Provided are methods of treating cancer that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRP? D1 domain variant and an Fc domain variant in combination with at least one chemotherapy agent and/or at least one therapeutic antibody. Also provided are related kits.

Abstract: The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglubulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

Abstract: Provided herein, inter alia, are isolated, humanized antibodies that bind an extracellular domain of a human SIRP-? polypeptide. Also provided are polynucleotides, vectors, host cells, and methods of production and use related thereto.

Abstract: Provided are methods of treating cancer (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), HER2-positive gastric/gastroesophageal junction (GEJ) cancer, de novo or transformed diffuse large B cell lymphoma (DLBCL), or indolent lymphoma) in an individual that comprise administering to the individual (a) a polypeptide comprising a SIRP? D1 domain variant and an Fc domain variant, and (b) an anti-cancer antibody (e.g., an anti-PD1 antibody, anti-HER2 antibody, or an anti-CD20 antibody). Also provided are related kits pharmaceutical compositions.