Abstract: The present disclosure provides CD19 binding molecules that specifically bind to CD19 including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD19 binding molecules, and pharmaceutical compositions comprising the CD19 binding molecules and the conjugates. The disclosure further provides methods of using the C19 binding molecules to treat diseases and disorders associated with expression of CD19. The disclosure yet further provides recombinant host cells engineered to express the CD19 binding molecules and methods of producing the CD19 binding molecules by culturing the host cells under conditions in which the CD19 binding molecules are expressed.

Abstract: The present disclosure provides CD19 binding molecules that specifically bind to CD19, including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD19 binding molecules, and pharmaceutical compositions comprising the CD19 binding molecules and the conjugates. The disclosure further provides methods of using the C19 binding molecules to treat diseases and disorders associated with expression of CD19. The disclosure yet further provides recombinant host cells engineered to express the CD19 binding molecules and methods of producing the CD19 binding molecules by culturing the host cells under conditions in which the CD19 binding molecules are expressed.

Abstract: The present disclosure features bifunctional compounds for the degradation of extracellular targets, as well as compositions and related methods thereof.

Abstract: The present disclosure provides CD2 binding molecules that specifically bind to CD2, including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD2 binding molecules, and pharmaceutical compositions comprising the CD2 binding molecules and the conjugates. The disclosure further provides methods of using the CD2 binding molecules to modulate CD2 signaling in order to treat a variety of immune (e.g., autoimmune), inflammatory and proliferative disorders. The disclosure yet further provides recombinant host cells engineered to express the CD2 binding molecules and methods of producing the CD2 binding molecules by culturing the host cells under conditions in which the CD2 binding molecules are expressed.

Abstract: The present invention features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the invention is based, in part, on the discovery that chimeric CD3 proteins (e.g., CD3delta, CD3gamma, and CD3 epsilon) having all or most of their extracellular domain fused to an antigen binding domain can activate the TCR in the presence of a cognate antigen. The invention is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion of the chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the invention include an antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.

Abstract: The present disclosure features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the disclosure is based, in part, on the discovery that chimeric CD3 proteins (e.g., CD3delta, CD3gamma, and CD3epsilon) having all or most of their extracellular domain fused to an antigen binding domain can activate the TCR in the presence of a cognate antigen. The disclosure is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion of the chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the disclosure include an antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.

Abstract: The present disclosure provides methods of treating a subject having a proliferative disease or an autoimmune disorder with a combination of (a) a first multispecific binding molecule (MBM) that binds specifically to (i) human CD2 and (ii) a human tumor-associated antigen and/or a human tumor microenvironment antigen, and (b) a second multispecific binding molecule that binds specifically to (i) a component of a human T-cell receptor (TCR) complex or a secondary T-cell signaling molecule and (ii) a human tumor-associated antigen and/or human tumor microenvironment antigen. The disclosure further provides MBMs and combinations of MBMs that can be used in the methods of the disclosure.

Abstract: The present disclosure provides CD2 binding molecules that specifically bind to CD2, including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD2 binding molecules, and pharmaceutical compositions comprising the CD2 binding molecules and the conjugates. The disclosure further provides methods of using the CD2 binding molecules to modulate CD2 signaling in order to treat a variety of immune (e.g., autoimmune), inflammatory and proliferative disorders. The disclosure yet further provides recombinant host cells engineered to express the CD2 binding molecules and methods of producing the CD2 binding molecules by culturing the host cells under conditions in which the CD2 binding molecules are expressed.

Abstract: Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Abstract: Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Abstract: The present disclosure provides multispecific binding molecules that specifically bind to a first tumor-associated antigen that is expressed on cancerous B cells, a second tumor-associated antigen that is expressed on cancerous B cells, and a component of a human T-cell receptor complex, conjugates comprising the trispecific binding molecules, and pharmaceutical compositions comprising the multispecific binding molecules and the conjugates. The disclosure further provides methods of using the multispecific binding molecules to treat cancers that express the tumor-associated antigens. The disclosure yet further provides recombinant host cells engineered to express the multispecific binding molecules and methods of producing the multispecific binding molecules by culturing the host cells under conditions in which the multispecific binding molecules are expressed.

Abstract: The present disclosure provides CD19 binding molecules that specifically bind to CD19, including monospecific, bispecific and trispecific binding molecules, conjugates comprising the CD19 binding molecules, and pharmaceutical compositions comprising the CD19 binding molecules and the conjugates. The disclosure further provides methods of using the C19 binding molecules to treat diseases and disorders associated with expression of CD19. The disclosure yet further provides recombinant host cells engineered to express the CD19 binding molecules and methods of producing the CD19 binding molecules by culturing the host cells under conditions in which the CD19 binding molecules are expressed.

Abstract: The present disclosure provides trispecific binding molecules that specifically bind to CD2, CD3 and a tumor-associated antigen, conjugates comprising the trispecific binding molecules, and pharmaceutical compositions comprising the trispecific binding molecules and the conjugates. The disclosure further provides methods of using the trispecific binding molecules to treat cancers that express the tumor-associated antigens. The disclosure yet further provides recombinant host cells engineered to express the trispecific binding molecules and methods of producing the trispecific binding molecules by culturing the host cells under conditions in which the trispecific binding molecules are expressed.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: The invention relates to the treatment of diseases associated with expression of BCMA, in particular myelomas. The invention relates to combination therapies of a BCMA CAR-expressing cell and a gamma secretase inhibitor.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Abstract: Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Abstract: Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Abstract: The present disclosure features the use of chimeric CD3 proteins to modulate T cell Receptor (TCR) signaling. Specifically, the disclosure is based, in part, on the discovery that chimeric CD3 proteins (e.g., CD3delta, CD3gamma, and CD3epsilon) having all or most of their extracellular domain fused to an antigen binding domain can activate the TCR in the presence of a cognate antigen. The disclosure is further based on the observation that the above chimeric proteins can be potentiated through the inclusion of a co-stimulatory domain in the intracellular portion of the chimeric molecule. Thus, the preferred elements of the engineered signaling complexes of the disclosure include an antigen binding domain, an extracellular domain derived from one of the above CD3 proteins, and an intracellular co-stimulatory domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.