Human or humanized tissues and organs suitable for transplant are disclosed herein. Gene editing of a host animal provides a niche for complementation of the missing genetic information by donor stem cells. Editing of a host genome to knock out or disrupt genes responsible for the growth and/or differentiation of a target organ and injecting that animal at an embryo stage with donor stem cells to complement the missing genetic information for the growth and development of the organ. The result is a chimeric animal in which the complemented tissue (human/humanized organ) matches the genotype and phenotype of the donor. Such organs may be made in a single generation and the stem cell may be taken or generated from the patient's own body. As disclosed herein, it is possible to do so by simultaneously editing multiple genes in a cell or embryo creating a niche for the complemented tissue. Multiple genes can be targeted for editing using targeted nucleases and homology directed repair (HDR) templates in vertebrate cells or embryos.

Expression vectors for rapid and high-throughput cloning, expression and screening of chimeric antigen receptor (CAR) constructs are provided.

The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

The present disclosure concerns dosages for the treatment of human patients susceptible to or diagnosed with a disease, such as cancer. Provided are methods for administering chimeric antigen receptor (CAR)-T cells. Also provided are compositions and articles of manufacture for use in the methods.

The present invention provides a method for activating a Natural Killer (NK) cell by contacting the NK cell in vitro with an activating tumor cell preparation (ATCP). The invention also provides an activated NK cell produced by such a method and its use in the treatment of cancer.

A method of treating a disease, such as cancer, by administering to a subject in need of such treatment an effective amount of allogeneic T cells with a MHC unrestricted chimeric receptor short time after partial lymphodepletion. The method also comprises administering one or more agents that delay egression of the allogeneic T cells from lymph nodes of said subject during adoptive transfer of said allogeneic T cells to the subject by trapping the T cells in the lymph nodes.

There is provided herein methods of treating leukemia or lymphoma in a subject in need thereof, with double negative T cells (DNTs) in combination with Interferon-.

The present invention is defined by the claims. In particular, the present invention relates to the use of TCR-deficient CAR-Tregs in combination with anti-TCR complex monoclonal antibodies for inducing durable tolerance.