Abstract: The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of the tumor microenvironment.

Abstract: Described herein are methods for producing and utilizing an artificial antigen presenting cell (aAPC). An aAPC is engineered to express a first and second chimeric stimulatory receptor that specifically bind antigen presenting on a T cell of interest. The aAPC as described herein is designed for use in activating and/or expanding a T cell or chimeric antigen receptor (CAR) T cell. Further, this invention relates to methods of treating cancer by administering to a subject in need thereof an aAPC-activated CAR T cell.

Abstract: Described herein are methods for producing and utilizing an alternative signal 1 domain to construct an optimally signaling CAR. Alternative signal 1 domains of the present technology are based on alternatives to CD3?, including mutated ITAMs from CD3? (which contains 3 IT AM motifs), truncations of CD3?, and alternative splice variants known as CD3s, CD3 theta, and artificial constructs engineered to express fusions between CD3s or CD30 and CD3?. CAR polypeptides comprising alternative signal 1 domains are utilized to engineer CAR T cells. Further, this technology related to methods of treating cancer by administering to a subject in need thereof CAR T cells comprising alternative signal 1 domains.

Abstract: Described herein are chimeric antigen receptors (CARs) targeting CD37, as well as related molecules and methods.

Abstract: Described herein are methods for producing and utilizing an artificial antigen presenting cell (aAPC). An aAPC is engineered to express a first and second chimeric stimulatory receptor that specifically bind antigen presenting on a T cell of interest. The aAPC as described herein is designed for use in activating and/or expanding a T cell or chimeric antigen receptor (CAR) T cell. Further, this invention relates to methods of treating cancer by administering to a subject in need thereof an aAPC-activated CART cell.

Abstract: Described herein are methods for producing and utilizing an alternative signal 1 domain to construct an optimally signaling CAR. Alternative signal 1 domains of the present technology are based on alternatives to CD3?, including mutated ITAMs from CD3? (which contains 3 IT AM motifs), truncations of CD3?, and alternative splice variants known as CD3s, CD3 theta, and artificial constructs engineered to express fusions between CD3s or CD30 and CD3?. CAR polypeptides comprising alternative signal 1 domains are utilized to engineer CAR T cells. Further, this technology related to methods of treating cancer by administering to a subject in need thereof CAR T cells comprising alternative signal 1 domains.

Abstract: In the disclosure provided herein are engineered immune cells (e.g., T cells) deficient in INFy expression and have reduced toxicity. Methods of producing the engineered immune cells (e.g., T cells) and methods of using the engineered immune cells (e.g., T cells) to treat cancer or autoimmune disease are also provided.

Abstract: Compositions and methods are provided for inhibiting T cell mediated destruction of virally transduced, trangene containing cells.

Abstract: Provided herein are CD70 targeting chimeric antigen receptors and engineered immune cells (e.g., T cells) comprising such CAR. Method of treating a cancer expressing CD70 using such engineered immune cells are also provided. In some embodiments, the method of treating cancer further comprising using an agent that enhances CD70 expression in the cancer (e.g., azacitidine) in combination with the engineered immune cells comprising the CD70-targeting CAR.

Abstract: 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.

Abstract: Described herein are chimeric antigen receptors (CARs) targeting CD37, as well as related molecules and methods.

Abstract: The present invention is directed to a chimeric antigen receptor (CAR) fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising VH and VL, wherein scFv binds to a tumor antigen, (ii) a transmembrane domain, (iii) a co-stimulatory domain of GITR intracellular domain, and (iv) an activating domain. In one embodiment, the tumor antigen is human epidermal growth factor receptor (EGFR), human mesothelin, or human CD19. CARs having GITR intracellular domain as a co-stimulatory domain have certain advantages over other traditional CAR co-stimulatory domains.

Abstract: Described herein are upfront methods for treating a patient suffering from a cancer. The method includes administering to the patient a therapeutically effective amount of an anti-cancer therapy including a chimeric antigen receptor (CAR) including an extracellular domain including a CD79b-binding domain and a CD19-binding domain, wherein the patient has not been previously treated for the cancer. The invention accordingly also relates to methods of producing and utilizing, e.g., T cells including CARs having an extracellular domain that binds CD79b and CD19.

Abstract: The technology described herein relates to modified T cells and their use in immunotherapeutic methods. In various examples, the T cells are modified so as to decrease or eliminate CD3?, TRAC, and/or TRBC expression.

Abstract: The technology described herein relates to vectors, isolated T cells, and methods of making and using the same, for example, in immunotherapeutic methods for T cell malignancies. In various examples, the T cells include a chimeric antigen receptor (CAR) that specifically binds to TRBC1 or TRBC2 and are modified so as to decrease or eliminate 003?, TRAC, and/or TRBC expression.

Abstract: The invention provides bispecific chimeric antigen receptors (CARs) targeting CD37 and CD19, as well as related molecules, immune cells including the same, compositions thereof, and their methods of use. The invention further provides methods for treating a disease or disorder, e.g., a cancer.

Abstract: The technology described herein relates to modified T cells and their use in immunotherapeutic methods. In various examples, the T cells are modified so as to decrease or eliminate OD3?, TRAC, and/or TRBC expression.

Abstract: Described herein are methods for producing and utilizing T cells comprising chimeric antigen receptors (CAR) comprising two or more extracellular domains, each comprising a portion of the extracellular domain of a Tumor Necrosis Factor (TNF) superfamily receptor ligand, e.g., A PRoliferation-Inducing Ligand (APRIL). The CARs described herein are capable of targeting, e.g., B cell maturation antigen (BCMA) and/or transmembrane activator and CAML interactor (TACI). Additionally, the CAR T cells of this present invention overcome resistance to anti-BCMA targeted therapies and utilize dimerizing and trimerizing transmembrane domains for optimal function. Further, this invention is related to methods of treating cancer (e.g., multiple myeloma (MM)), plasma cell diseases or disorders, autoimmune diseases or disorders, or transplant rejection.

Abstract: The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of a tumor microenvironment. The invention provides chimeric antigen receptors (CARs) that target a tumor microenvironment. In one aspect, the invention features an immune cell engineered to express: (a) a chimeric antigen receptor (CAR) polypeptide including an extracellular domain including a first antigen binding domain that binds to a first antigen and a second antigen-binding domain that binds to a second antigen; and (b) a bispecific T cell engager (BiTE), wherein the BiTE binds to a target antigen and a T cell antigen. In another aspect, the invention features a pharmaceutical composition including the immune cell. In another aspect, the invention features a method of treating a cancer in a subject in need thereof, the method comprising administering the immune cell.

Abstract: The invention provides herein engineered regulatory T cells (Tregs), compositions thereof, and their methods of use. The Tregs described herein can be engineered to include, e.g., a chimeric antigen receptor (CAR), conferring increased stability, specificity, and immunosuppressive activity towards a target antigen. Furthermore, Tregs can also be engineered to reduce T cell cytotoxicity functions. Also provided are methods of suppressing immune response against a specific target antigen using the engineered Tregs described herein.