The following are disclosed: a method for producing a T cell progenitor, including step (1) of culturing CD34.sup.+ cell in a medium containing an aryl hydrocarbon receptor antagonist, a medium for T cell progenitor differentiation containing an aryl hydrocarbon receptor antagonist, and a T cell progenitor inducer containing an aryl hydrocarbon receptor antagonist.

The present disclosure provides methods for treating cancer and infectious disease using manufactured T cells or other cell types including antigen-presenting T cells, loaded, antigen-presenting T cells, sensitized, manufactured T cells and combinations thereof which can be co-administered with the manufactured T cells or without. Methods of treatment can include administration of pentostatin and cyclophosphamide followed by administration of T cells. The present disclosure also provides methods to produce antigen-presenting T cells from the manufactured T cells, load said antigen-presenting T cells and to sensitize the manufactured T cells using the loaded, antigen-presenting T cells. Methods of treatment using the antigen-presenting T cells and/or sensitized, manufactured T cells are also provided which can be performed in vivo or ex vivo.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.

Provided are methods for generating γδ T cells from induced pluripotent stem cells. Also provided are genetically engineered iPSCs, γδ T cells, CAR-γδ T cells, and methods of using the same.

Provided are method for generating αβ T cells from induced pluripotent stem cells. Also provided are genetically engineered iPSCs, αβ T cells, CAR-αβ T cells, and methods of using the same.

In some embodiments, methods of delivering a therapeutically effective amount of an expanded number of tumor infiltrating lymphocytes obtained from tumor remnants to a patient in need thereof, for the treatment of a cancer, are disclosed.

Methods for activating and expanding TILs using unconventional cytokines are provided. These methods include techniques for activating and expanding TILs using streamlined approaches, including one-step approaches, approaches using agonists for stimulation, approaches more suitable for clinical manufacturing, and approaches without the requirement of feeder cells, are provided. Compositions of expanded populations of TILs are also provided, in addition to populations of expanded TILs enriched in central memory T cell phenotype.

Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Safe, rapid and efficient methods for producing antigen-specific T cells recognizing human papilloma virus or HPV antigens.