A vector comprising a first polynucleotide encoding a FOXP3 polypeptide and a second polynucleotide encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen recognition domain which specifically binds to a human leukocyte antigen (HLA), wherein the first polynucleotide and the second polynucleotide are operably linked to the same promoter, and wherein the first polynucleotide is upstream of the second polynucleotide.

The present is directed to compositions comprising regulatory T cell epitopes, wherein said epitopes comprise a polypeptide comprising at least a portion of SEQ NOS: 1-73, fragments and/or variants thereof, as well as methods of producing and using the same.

Provided are novel fusion proteins, nucleic acids encoding said proteins, vectors comprising said nucleic acids, compositions comprising said nucleic acids or vectors, host cells comprising said nucleic acids, vectors or compositions or pharmaceutical compositions. Provided are methods of reducing (down regulating) a target membrane-bound protein (MBP) level in a cell, methods of producing a cell having a reduced target membrane-bound protein level, or methods of treating a disease, or methods of reducing or preventing GvHD in a subject associated with the administration of one or more CAR T-cells to the subject.

Provided is an engineered T cell. The expression of a TCR/CD3 complex on the cell surface is reduced by means of introducing a polypeptide that down-regulates the expression of the TCR/CD3 complex on the cell surface into the cell. The engineered T cell can be used for therapeutic purposes, such as treatment of cancers.

Provided herein, inter alia, are compositions and methods for reprogramming immune cells for treating or preventing immune disorders. The methods include contacting immune cells with antigens, and administering the resultant immune cells to a subject who has an immune disorder.

Aspects of the present disclosure relate to methods and compositions related to the preparation of immune cells, including engineered immune cells. Certain embodiments of the disclosure include compositions, cells, and methods related to engineered invariant natural killer T (iNKT) cells for off-the-shelf use for clinical therapy. The iNKT cells may be produced from hematopoietic stem progenitor cells and may be suitable for allogeneic cellular therapy because they are HLA negative. In some aspects, the cells have imaging and suicide targeting capabilities.

The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

Antibody-mediated rejection (ABMR) is one of the main obstacles to successful transplantation, including ABO blood group-incompatible (ABOi) transplantation. C4d deposition is a marker of ABMR and is also found in most ABOi allograft tissues. Described herein are anti-C4d CAR Tregs that suppress ABMR in ABOi allografts. Anti-C4d CAR Tregs prepared by retroviral transduction of CAR into CD62L +CD4 +CD25 +Tregs, expressed Foxp3, CD25, CTLA-4, LAP, and GITR to similar extents as non-transduced Tregs. Anti-C4d CAR Tregs were activated by specific binding to C4d and suppressed in vitro T cell proliferation as well as non-transduced Tregs. Furthermore, adoptive transfer of anti-C4d CAR Tregs significantly prolonged mouse ABOi heart allograft survival (P<0.05).

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

The inventors explored in an allogeneic situation the regulatory potential of Mucosal-Associated Invariant T cells (MAIT cells), a population of unconventional T cells that exhibit potent antibacterial activity, expressing a semi-invariant TCR which recognizes vitamin B2 derivatives of microbial origin presented by the MR1 molecule. In particular, the inventors used i) an allogenic reaction model in vitro (mixed lymphocyte reaction, MLR) and ii) murine model of xenogeneic aGvHD They first verified that human MAIT cells do not proliferate in response to allogeneic stimulation in vitro (MLR) or in vivo (immunodeficient mice) alone but require for their expansion both an inflammatory environment and TCR ligation by its ligand. In contrast, MAIT cells are able to inhibit the proliferation of allospecific LT in vitro in a dose-dependent manner. Furthermore, the adoptive transfer of MAIT cells in a mouse model of xeno-GVHD resulted in a delay in early or late GvHD development. Altogether, these data describe a new regulatory function of MAIT cells in an allogeneic context, allowing us to consider their use in cell therapy to limit GvHD.