The present disclosure provides bispecific chimeric antigen receptors targeting CD20 and BCMA. The CAR may comprise an scFv targeting CD20 and an scFv targeting BCMA, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasmic signaling domain. The chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

The present disclosure relates to BCMA/CD19 CAR T-cell products and methods for treating relapsed or refractory BCMA+ or CD19+ malignancies.

Provided herein are biepitopic or bispecific chimeric antigen receptors. The chimeric antigen receptors comprise a combination of single domain antibody mimics. The single domain antibody mimics may be monobodies, affibodies, or DARPins. The disclosed chimeric antigen receptors may recognize two different epitopes of the same tumor antigen. For example, the chimeric antigen receptor may recognize two different epitopes of HER-2 or EGFR. The disclosed chimeric antigen receptors may recognize two epitopes of two different tumor antigens. For example, the chimeric antigen receptor may recognize HER-2 and EGFR. The disclosed chimeric antigen receptors may be expressed in immune cells for use in cancer immunotherapy.

Provided herein are multiplexed T cell receptor compositions, combination therapies, and uses thereof.

This invention is directed to engineered cells and methods for using the same. In embodiments, the engineered cell comprises a nucleic acid encoding a chimeric antigen receptor and a polypeptide, wherein the chimeric antigen receptor is specific for two or more antigens on the surface of a cancer cell, and wherein the polypeptide comprises an antibody or fragment thereof that can be secreted from the engineered cell.

Provided herein are methods for manufacturing CAR-T cell products with high purity of TSCM subsets (>90%), independent of the variations from incoming leukapheresis. In some embodiments, to isolate the CCR7 and CD45RA double positive T cell subset, the processes described herein deplete CD45RO positive cells from leukapheresis and positively enrich for a CD4 and CD8 T cell population to isolation both TSCM and effector memory T cell (TEMRA) subsets, both of which positively express CD45RA and CCR7.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

The present disclosure provides adoptive T cell therapies that have improved architectures for targeting antigens and recruiting multimeric immune signaling complexes for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Transgenic T cells and vectors for making transgenic T cells are described. The vectors can include a nucleic acid encoding a membrane-bound anti-IL6 (mb-alL6) single chain variable fragment (scFv), and the transgenic T cells can express mb-alL6. The transgenic T cells are useful for suppressing proliferation of IL-6-dependent cells, reducing IL-6 concentration, or both. In one embodiment, the vector is a bicistronic construct encoding the mb-alL6 and an anti-CD19-41 BB-003 chimeric antigen receptor (CAR). In another embodiment, an anti-IL-6 scFv can be linked to a 41 BB and 003 domains to form an anti-IL-6 CAR. The transgenic T cells expressing said constructs can reduce the linker risk of cytokine release syndrome (CRS) in cancer patients being treated with CAR T cell or for the treatment of autoimmune diseases and inflammatory diseases in which cytokines are involved in pathogenesis.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.