B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides novel bispecific antibodies (bsAbs) that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing tumor cells. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing BCMA. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced BCMA-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing mono- and/or bi-specific chimeric antigen receptors (CAR) with anti-CD133 and anti-EGFR antigen binding domains, and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

The disclosure provides synthetic immune receptors (SIRs), nucleic acids encoding the SIRs, methods of making and using the SIRs, in, for example, adoptive cell therapy.

The present disclosure provides compositions and methods for making and using engineered killer phagocytic cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, the chimeric receptor is encoded by a recombinant nucleic acid.

The invention relates to novel chimeric antigen (CAR) mRNA molecules, the methods of generating the molecules and methods of treating cancer with the molecules.

Provided herein are antibodies and antigen-binding fragment thereof targeting CLL1, and chimeric antigen receptors (e.g., monovalent CAR, and multivalent CAR including bi-epitope CAR) having one or more anti-CLL1 antigen-binding fragments thereof. Further provided are engineered immune effector cells (e.g., T cells) expressing the chimeric antigen receptors and methods of use thereof.

Provided herein are antibodies and antigen-binding fragment thereof targeting CD33, and chimeric antigen receptors (e.g., monovalent CAR, and multivalent CAR including bi-epitope CAR) having one or more anti-CD33 antigen-binding fragments thereof. Further provided are engineered immune effector cells (e.g., T cells) expressing the chimeric antigen receptors and methods of use thereof.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express cytotoxic chimeric receptors and various dosing regimens for administering such cells. In several embodiments, the immune cells express a chimeric receptor that targets ligands of NKG2D on tumor cells. In several embodiments, the cancer is a blood cancer, for example, acute myeloid leukemia (e.g., relapsed/refractory acute myeloid leukemia) or myelodysplastic syndrome. In several embodiments, the tumor is a solid tumor, for example, intrahepatic cholangiocarcinoma or other liver tumor, for example, secondary metastases from colorectal cancer.

Aspects of the present disclosure include methods and compositions related to therapeutic immune cells having enhanced metabolic fitness. In certain aspects, polynucleotides encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism and, optionally, one or more antigen-specific receptors, are disclosed. In some aspects, disclosed are methods for enhancing the metabolic fitness of an immune cell comprising introducing into the immune cell a polynucleotide encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism. Cells (e.g., NK cells, T cells) expressing polynucleotides encoding one or more viral, bacterial, and/or fungal genes capable of manipulating cell metabolism and, optionally, one or more antigen-specific receptors are described. Also described are therapeutic methods using polynucleotides of the disclosure.

The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.