Abstract: Antibodies that specifically bind to CD47 and antibodies that specifically bind to PD-L1 are provided, as well as CD47/PD-L1 bispecific antibodies. Also provided are uses of these antibodies, and related compositions and methods.

Abstract: Provided herein are anti-idiotype antibodies that specifically recognize anti-BCMA antibody moieties, in particular, anti-BCMA antibody moieties present in recombinant receptors, including chimeric antigen receptors (CARs). The disclosure further relates to uses of anti-idiotype antibodies for specifically identifying and/or selecting cells expressing such recombinant receptors, such as anti-BCMA CAR T cells. The disclosure further relates to uses of anti-idiotype antibodies for specifically activating such cells.

Abstract: The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Abstract: The present invention relates to antibodies, e.g., full length antibodies or antigen binding fragments thereof, that specifically bind to BCMA (B-Cell Maturation Antigen) and/or CD3 (Cluster of Differentiation 3). The invention also relates to antibody conjugates (e.g., antibody-drug-conjugates) comprising the BCMA antibodies, compositions comprising the BCMA antibodies, and methods of using the BCMA antibodies and their conjugates for treating conditions associated with cells expressing BCMA (e.g., cancer or autoimmune disease). The invention further relates to heteromultimeric antibodies that specifically bind to CD3 and a tumor cell antigen, (e.g., bispecific antibodies that specifically bind to CD3 and BCMA). Compositions comprising such heteromultimeric antibodies, methods for producing and purifying such heterodimeric antibodies, and their use in diagnostics and therapeutics are also provided.

Abstract: Provided herein are PD-1 chimeric cytokine receptors. When present on chimeric antigen receptor (CAR)-bearing immune cells, such receptors allow for increased immune cell activation, proliferation, persistence, and/or potency, when engaged with PD-1 ligands or activation with an anti-PD-1 antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Abstract: The present invention relates to antibodies, e.g., full length antibodies or antigen binding fragments thereof, that specifically bind to BCMA (B-Cell Maturation Antigen) and/or CD3 (Cluster of Differentiation 3). The invention also relates to antibody conjugates (e.g., antibody-drug-conjugates) comprising the BCMA antibodies, compositions comprising the BCMA antibodies, and methods of using the BCMA antibodies and their conjugates for treating conditions associated with cells expressing BCMA (e.g., cancer or autoimmune disease). The invention further relates to heteromultimeric antibodies that specifically bind to CD3 and a tumor cell antigen, (e.g., bispecific antibodies that specifically bind to CD3 and BCMA). Compositions comprising such heteromultimeric antibodies, methods for producing and purifying such heterodimeric antibodies, and their use in diagnostics and therapeutics are also provided.

Abstract: Provided herein are PD-1 chimeric cytokine receptors. When present on chimeric antigen receptor (CAR)-bearing immune cells, such receptors allow for increased immune cell activation, proliferation, persistence, and/or potency, when engaged with PD-1 ligands or activation with an anti-PD-1 antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Abstract: Provided herein are DLL3 binding agents and chimeric antigen receptors (CARs) comprising a DLL3 binding molecule that specifically binds to DLL3; and immune cells comprising these DLL3-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using DLL3-specific CARs, and immune cells comprising DLL3-specific CARs.

Abstract: Antibodies that specifically bind to CD47 and antibodies that specifically bind to PD-L1 are provided, as well as CD47/PD-L1 bispecific antibodies. Also provided are uses of these antibodies, and related compositions and methods.

Abstract: Provided herein are antibodies with conditional affinity for an antigen. The affinity of an antibody with conditional affinity for an antigen may be altered by a small molecule agent. Antibodies with conditional affinity may be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

Abstract: Provided herein are DLL3 binding agents and chimeric antigen receptors (CARs) comprising a DLL3 binding molecule that specifically binds to DLL3; and immune cells comprising these DLL3-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using DLL3-specific CARs, and immune cells comprising DLL3-specific CARs.

Abstract: The present invention provides antibodies that specifically bind to CD70 (Cluster of Differentiation 70). The invention further provides bispecific antibodies that bind to CD70 and another antigen (e.g., CD3). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific). The invention further relates to therapeutic methods for use of these antibodies for the treatment of CD70-mediated pathologies, including cancer.

Abstract: Provided herein are CD70-binding proteins comprising a CD70-binding domain and a transmembrane domain, engineered immune cells comprising the CD70-binding proteins, and methods of making and using the same. Also provided herein are engineered immune cells e.g. CAR (chimeric antigen receptor) T cells for administration to patients to treat cancer (e.g., solid tumors and hematologic tumors) and other unwanted conditions. The cells are engineered to functionally express a first antigen binding molecule e.g. a CD70 CAR and a second antigen binding molecule e.g. a second CAR that binds a target molecule characteristic of the cancer or other disease or unwanted condition. The cells may be further engineered to reduce the functional expression level of one or more of TRAC, CD52 and CD70. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering them.

Abstract: The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Abstract: Compositions, methods, expression vectors and engineered immune cells for improving therapies that entail the administration of allogeneic cells to a patient. An immune cell, e.g., a T cell, modified to comprise and/or express FasL protein or a FasL protein derivative from, for example, an expression vector comprising a polynucleotide that encodes FasL protein or a FasL protein derivative, and to express FasR at a reduced level, and further modified to comprise and/or express an antigen binding protein e.g., a chimeric antigen receptor (CAR). An improved method of CAR T-cell therapy that comprises administering the improved immune cells, and compositions that comprise the improved immune cells. Methods of improving persistence of administered cells and reducing activation-induced cell death comprising administering the improved cells.

Abstract: Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, ?2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and/or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Abstract: Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

Abstract: The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

Abstract: A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

Abstract: The present invention provides antibodies that specifically bind to CD70 (Cluster of Differentiation 70). The invention further provides bispecific antibodies that bind to CD70 and another antigen (e.g., CD3). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific). The invention further relates to therapeutic methods for use of these antibodies for the treatment of CD70-mediated pathologies, including cancer.