The invention provides antibodies, antibody-drug conjugates, bispecific T cell engagers (BiTEs), and chimeric antigen receptors (CARs) that target transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Such antibodies, antibody-drug conjugates, BiTEs, and CARs can be used, e.g., in methods for treating a cancer (e.g., multiple myeloma), an autoimmune disorder (e.g., characterized by a high titer of antibodies contributing to the disorder), or a plasma cell disease disorder (e.g., plasma cell dyscrasias) in a subject in need thereof.

The present invention relates to antigen-based immunotherapy, in particular cancer immunotherapy. In particular, the present invention provides antigenic peptides, which are distinct from, but have amino acid similarity to, especially share the same core sequence with epitopes of human tumor antigens. The present invention further provides immunogenic compounds, nanoparticles, cells and pharmaceutical compositions comprising such antigenic peptides and nucleic acids encoding such antigenic peptides.

Provided herein are BCMA CARs and CAR-T cells, gamma secretase inhibitors, and the combination thereof. Also provided are the combination of BCMA CAR-T cells and gamma secretase inhibitors for use in treating cancer. In some embodiments, particular dosing regimens, redosing regimens, and combination regimens with lymphodepletion are provided, for the treatment and clinical management of multiple myeloma in subjects in need thereof.

Provided herein are BCMA CARs and CAR-T cells, gamma secretase inhibitors, and the combination thereof. Also provided are the combination of BCMA CAR-T cells and gamma secretase inhibitors for use in treating cancer. In some embodiments, particular dosing regimens, redosing regimens, and combination regimens with lymphodepletion are provided, for the treatment and clinical management of multiple myeloma in subjects in need thereof.

The disclosure provides compositions and methods for for modifying an endogenous cell surface protein (e.g., an endogenous TCR) in a cell (e.g., a T cell) with a CAR or an exogenous protein (e.g., an exogenous intracellular or cell surface protein (e.g., an exogenous TCR)).

Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

An antibody specifically binding to BCMA and an antigen binding fragment thereof, a chimeric antigen receptor (CAR) containing the antigen binding fragment, a nucleic acid molecule encoding the CAR, an immune effect cell expressing the CAR, a method for preparing the immune effect cell, use of the CAR and the immune effect cell for preventing and/or treating a B cell-related disease (for example, a B-cell malignancy and an autoimmune disease), and a method for preventing and/or treating the B cell-related disease.

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 application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, shRNAs designed to downregulate CD52 are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy, especially in combination with immunosuppressive therapies directed against CD52, as is particularly envisaged in allogeneic therapy. The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. Further, strategies to treat diseases such as cancer using these cells are also provided. The engineered immune cells, such as T-cells or natural killer (NK) cells, expressing such CARs are particularly suitable for treating lymphomas, multiple myeloma and leukemia.

The present application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, shRNAs designed to downregulate CD52 are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy, especially in combination with immunosuppressive therapies directed against CD52, as is particularly envisaged in allogeneic therapy. The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. Further, strategies to treat diseases such as cancer using these cells are also provided. The engineered immune cells, such as T-cells or natural killer (NK) cells, expressing such CARs are particularly suitable for treating lymphomas, multiple myeloma and leukemia.