Abstract: B-cell maturation antigen (BCMA) is expressed on plasma cells. The present invention provides methods for desensitizing patients in need of a solid organ transplant to anti-HLA antibodies using bispecific antibodies that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing plasma cells. In certain embodiments, the bispecific antibodies of the present invention reduce alloantibody levels and/or reduce calculated panel reactive antibody levels to facilitate solid organ transplantation and/or improve long term graft survival and/or function.

Abstract: The present invention provides novel full-length human antibodies that bind to human Fc epsilon-R1 alpha (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both Fc epsilon-R1 alpha and CD3 and activate T cells via the CD3 complex in the presence of Fc epsilon-R1 alpha-expressing cells. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced Fc epsilon-R1 alpha-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of allergies, including anaphylaxis.

Abstract: Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. The methods use CD40 inhibitors (e.g., CD40 antigen-binding molecules) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

Abstract: Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. Some methods, such as when a subject has preexisting against an immunogen to be administered, use plasma cell depleting agents or combinations comprising plasma cell depleting agents to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

Abstract: The present disclosure provides compositions and methods for inhibiting or preventing an immune response to an immunogen (e.g., an immunogenic delivery vehicle) in a subject in need thereof, comprising administering to the subject an effective amount of a plasma cell depleting agent, e.g., an antigen-binding molecule that binds to B cell maturation antigen (BCMA) and cluster of differentiation 3 (CD3) (e.g., an anti-BCMA×CD3 bispecific antibody, or a functional fragment thereof) or a B cell depleting agent, e.g., an antigen-binding molecule that binds to CD20 and CD3 (e.g., an anti-CD20×CD3 bispecific antibody, or a functional fragment thereof), either alone or in combination with one another, and/or in combination with an immunoglobulin depleting agent such as a neonatal fragment crystallizable (Fc) receptor (FcRn) blocker (e.g., efgartigimod).

Abstract: The present disclosure provides methods for treating allergy comprising selecting a patient with an allergy and administering a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor (e.g., an anti-IL-4 receptor antibody or antigen-binding fragment thereof) in combination with a therapeutically effective amount of an agent that depletes plasma cells (e.g., an anti-BCMA/anti-CD3 bispecific antibody). In certain embodiments, a plasma cell ablating agent such as an anti-BCMA/anti-CD3 bispecific antibody ablates the plasma cells, including IgE+ plasma cells, while the IL-4/IL-13 pathway inhibitor prevents the generation of new IgE+ plasma cells, thus eliminating allergen-specific IgE in the patient.

Abstract: The present disclosure provides methods for treating allergy comprising selecting a patient with an allergy and administering a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor (e.g., an anti-IL-4 receptor antibody or antigen-binding fragment thereof) in combination with a therapeutically effective amount of an agent that depletes plasma cells (e.g., an anti-BCMA/anti-CD3 bispecific antibody). In certain embodiments, a plasma cell ablating agent such as an anti-BCMA/anti-CD3 bispecific antibody ablates the plasma cells, including IgE+ plasma cells, while the IL-4/IL-13 pathway inhibitor prevents the generation of new IgE+ plasma cells, thus eliminating allergen-specific IgE in the patient.

Abstract: The present invention provides novel full-length human antibodies that bind to human Fc epsilon-R1 alpha (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both Fc epsilon-R1 alpha and CD3 and activate T cells via the CD3 complex in the presence of Fc epsilon-R1 alpha-expressing cells. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced Fc epsilon-R1 alpha-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of allergies, including anaphylaxis.

Abstract: The present invention provides novel full-length human antibodies that bind to human Fc epsilon-R1 alpha (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both Fc epsilon-R1 alpha and CD3 and activate T cells via the CD3 complex in the presence of Fc epsilon-R1 alpha-expressing cells. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced Fc epsilon-R1 alpha-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of allergies, including anaphylaxis.

Abstract: The present disclosure provides methods for treating allergy comprising selecting a patient with an allergy and administering a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor (e.g., an anti-IL-4 receptor antibody or antigen-binding fragment thereof) in combination with a therapeutically effective amount of an agent that depletes plasma cells (e.g., an anti-BCMA/anti-CD3 bispecific antibody). In certain embodiments, a plasma cell ablating agent such as an anti-BCMA/anti-CD3 bispecific antibody ablates the plasma cells, including IgE+ plasma cells, while the IL-4/IL-13 pathway inhibitor prevents the generation of new IgE+ plasma cells, thus eliminating allergen-specific IgE in the patient.

Abstract: The present invention provides novel full-length human antibodies that bind to human Fc epsilon-R1 alpha (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both Fc epsilon-R1 alpha and CD3 and activate T cells via the CD3 complex in the presence of Fc epsilon-R1 alpha-expressing cells. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced Fc epsilon-R1 alpha-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of allergies, including anaphylaxis.