Abstract: The invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-? 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: 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 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 decoy polypeptides comprising: (a) a SIRP? variant, a SIRP?1 variant, or a SIRP?2 variant, and (b) a human Fc variant comprising at least one amino acid substitution that reduces effector function compared to a wild type human Fc. Also provided are methods of using such decoy polypeptides, and chimeric molecules comprising such polypeptides.

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: Provided are methods of reducing and/or preventing interference by a drug comprising (i) an antibody Fc region and (ii) a moiety that binds to human CD47 in serological assays.

Abstract: The invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-? 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 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 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: 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 disclosure features signal-regulatory protein a (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 a (SIRP-?) D1 variant and (ii) an antibody.

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 invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-? 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: 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: 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 invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-? 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 invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-? 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.