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 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 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 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 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: 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 disclosure features compositions and methods for treating a metabolic disorder, including diabetes, conditions associated with inhibition of insulin secretion, or for increasing longevity. In some embodiments, the methods comprise administering an anti-CGRP antagonist 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.

Abstract: A novel class of proteins, semaphorins, nucleic acids encoding semaphorins, semaphorin peptides, and methods of using semaphorins and semaphorin-encoding nucleic acids are disclosed. Semaphorin peptides and receptor agonists and antagonists provide potent modulators of nerve cell growth and regeneration. The invention provides pharmaceutical compositions, methods for screening chemical libraries for regulators of cell growth/differentiation; semaphorin gene-derived nucleic acids for use in genetic mapping, as probes for related genes, and as diagnostic reagents for genetic neurological disease; specific cellular and animal systems for the development of neurological disease therapy.

Abstract: Disclosed are methods and compositions for identifying agents which modulate the interaction of Robo and a Robo ligand and for modulating the interaction of Robo and a Robo ligand. The methods for identifying Robo:ligand modulators find particular application in commercial drug screens. These methods generally comprise (1) combining a Robo polypeptide, a Slit polypeptide and a candidate agent under conditions whereby, but for the presence of the agent, the Robo and Slit polypeptides engage in a first interaction, and (2) determining a second interaction of the Robo and Slit polypeptides in the presence of the agent, wherein a difference between the first and second interactions indicates that the aget modulates the interaction of the Robo and Slit polypeptides.

Abstract: Robo1 and Robo2 polypeptides may be produced recombinantly from transformed host cells from the disclosed Robo encoding nucleic acids or purified from human cells. The invention provided isolated Robo hybridization probes and primers capable of specifically hybridizing with the disclosed Robo genes, Robo-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.