Chimeric antigen receptors with an antibody-binding domain are presented that are preferably expressed from a recombinant cell in a therapeutic cell, and particularly in an NK-92 cell or derivative thereof. Notably, such modified cells have multiple modes of cytotoxicity, improved on-target cell killing, decreased off-target cell killing, show significant expression of the recombinant CAR, and/or increased CAR-mediated cytotoxicity.

A method efficiently produces cytotoxic T lymphocytes having intrinsic properties of lymphocytes of the acquired immune system suitable for cellular immunotherapy. The method includes culturing CD4/CD8 double-positive T cells in a medium containing IL-7 and a T-cell receptor activator, to induce CD8.sup.+.sup.+ cytotoxic T lymphocytes.

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.

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.

The present disclosure provides methods for genetically modifying and expanding immune cells ex vivo, especially for use in cell-based adoptive immunotherapy. As such, method embodiments are provided for transducing immune cells (e.g. T cells and/or NK cells) that include a step of activating the cells and genetically modifying the activated cells, for example by transducing the cells with recombinant retroviral particles, such as lentiviral particles. Genetically modified cells produced by these methods are also provided. Such methods are typically performed within a closed system, and in illustrative embodiments within a single chamber of a closed system. The methods typically include expanding the genetically modified immune cells in cell expansion media within the closed system, in illustrative embodiments within the single chamber of the closed system. As such, provided herein in illustrative embodiments, are fed-batch, single-reactor method systems.

Disclosed herein are methods for culturing CAR-modified immune cells with at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Disclosed herein are methods for culturing CAR-modified immune cells with at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Described herein are methods of promoting engraftment of a cell transplant and methods of killing hematopoietic stem cells by administering a population of T cells, NK cells or cytotoxic immune effector cells comprising a cell-surface receptor for a stem cell-specific antigen. Also described herein is a composition comprising T cells, NK cells or cytotoxic immune effector cells genetically modified to encode a cell-surface receptor for a stem cell-specific antigen.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present disclosure provides, among other things, a method for efficiently producing a cell population enriched in Natural Killer cells (NK cells) from induced pluripotent cells.