Abstract: Provided are methods, uses, and articles of manufacture of combination therapies involving immunotherapies and cell therapies, such as adoptive cell therapy, e.g. a T cell therapy, and the use of an inhibitor of a prosurvival BCL2 family protein, e.g. a BCL2 inhibitor, for treating subjects having or suspected of having a cancer, and related methods, uses, and articles of manufacture. The T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs).

Abstract: Provided herein are methods for producing engineered T cells that express a recombinant receptor, such as for use in cell therapy. In some aspects, the provided methods include one or more steps for incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and/or cultivating the cells under conditions that promote proliferation and/or expansion, in which one or more steps is carried out in the presence of an agent that inhibits mammalian target of rapamycin (mTOR) activity. In some aspects, cultivation is performed in the presence of an agent that inhibits mammalian target of rapamycin (mTOR) activity. In some aspects, the provided methods produce genetically engineered T cells with improved persistence and/or anti-tumor activity in vivo.

Abstract: Provided are chimeric receptors for engineering cells for adoptive therapy, including T cells, and the genetically engineered cells. In some embodiments, the chimeric receptors, such as chimeric antigen receptors (CARs) are modified in a junction region by one or more amino acid modifications such that peptide fragments of such region exhibit a lower binding affinity for a human leukocyte antigen (HLA) and/or the region exhibits reduced immunogenicity, including following administration to a subject. In some aspects, also provided are methods and compositions for engineering and producing cells expressing such chimeric receptors, compositions containing the cells, and method for their administration to subjects. In some embodiments, features of the chimeric receptors and engineered cells containing the chimeric receptors result in methods that provide for increased or improved activity, efficacy and/or persistence.

Abstract: Provided are chimeric receptors for engineering cells for adoptive therapy, including T cells, and the genetically engineered cells. In some aspects, also provided are methods and compositions for engineering and producing the cells, compositions containing the cells, and method for their administration to subjects. In some embodiments, the cells, such as T cells, contain genetically engineered antigen receptors that specifically bind to antigens, such as a chimeric antigen receptor (CAR), and which contain an intracellular signaling domain capable of inducing TRAF6-mediated signaling. In some embodiments, features of the cells and methods provide for increased or improved activity, efficacy and/or persistence.