Provided herein, inter alia, are PD-L1(+) natural killer cells that express soluble IL-15, PD-L1(+) natural killer cells that express soluble IL-15 and truncated EGFR, and methods of treating cancer using the PD-L1(+) natural killer cells. In an aspect is provided a method of treating cancer in a patient in need thereof comprising administering to the patient an effective amount of PD-L1(+) natural killer cells that express soluble IL-15.

Provided herein, inter alia, are PD-L1(+) natural killer cells that express soluble IL-15, PD-L1(+) natural killer cells that express soluble IL-15 and truncated EGFR, and methods of treating cancer using the PD-L1(+) natural killer cells. In an aspect is provided a method of treating cancer in a patient in need thereof comprising administering to the patient an effective amount of PD-L1(+) natural killer cells that express soluble IL-15.

The present disclosure provides a population of poly-donor CD4.sup.IL-10 cells generated by genetically modifying CD.sup.4+ T cells from at least three different T cell donors. Further provided are methods of generating the poly-donor CD4.sup.IL-10 cells and methods of using the poly-donor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and other immune disorders.

The present disclosure provides a population of poly-donor CD4.sup.IL-10 cells generated by genetically modifying CD.sup.4+ T cells from at least three different T cell donors. Further provided are methods of generating the poly-donor CD4.sup.IL-10 cells and methods of using the poly-donor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and other immune disorders.

Described are immune cells expressing a chimeric antigen receptor targeted to EGFR and having an oxygen-dependent degradation domain. The chimeric antigen receptor is co-expressed in immune cells, e.g., NK cells with a soluble form of human IL-15. The inclusion of an oxygen-dependent degradation domain substantially restricts the activity of the immune cells expressing the chimeric antigen receptor to the more hypoxic environment of solid tumor tissue. The NK cells expressing the chimeric antigen receptor are useful for treating breast cancer that has low or no HER2 expression.

Described are immune cells expressing a chimeric antigen receptor targeted to EGFR and having an oxygen-dependent degradation domain. The chimeric antigen receptor is co-expressed in immune cells, e.g., NK cells with a soluble form of human IL-15. The inclusion of an oxygen-dependent degradation domain substantially restricts the activity of the immune cells expressing the chimeric antigen receptor to the more hypoxic environment of solid tumor tissue. The NK cells expressing the chimeric antigen receptor are useful for treating breast cancer that has low or no HER2 expression.

The present invention provides a method for producing a T cell from an induced pluripotent stem cell, wherein the induced pluripotent stem cell is derived from a cell other than an T cell.

The present invention relates to a targeting module comprising at least one CD123-binding domain and a tag-binding domain binding the human La epitope E5B9, a nucleic acid, a vector or a cell comprising a nucleotide sequence encoding the targeting module, a pharmaceutical composition and a kit comprising the targeting module and a vector or a cell comprising a nucleotide sequence encoding a reversible chimeric antigen receptor.

Provided herein, amongst other things, are polynucleotides comprising a) a chimeric antigen receptor (CAR) comprising: an extracellular antigen binding domain comprising an antibody or antigen binding fragment thereof; a transmembrane region; and an intracellular signaling region comprising an OX40L intracellular signaling domain; and b) a nucleic acid encoding an IL-15.

Provided herein, amongst other things, are polynucleotides comprising a) a chimeric antigen receptor (CAR) comprising: an extracellular antigen binding domain comprising an antibody or antigen binding fragment thereof; a transmembrane region; and an intracellular signaling region comprising an OX40L intracellular signaling domain; and b) a nucleic acid encoding an IL-15.