The present invention relates to a cell-based medicine comprising mesenchymal stem cells, and a method for producing the same. More specifically, the present invention relates to: a cell-based medicine containing mesenchymal stem cells, wherein a) the mesenchymal stem cells express CX3CL1 under stimulation with an inflammatory cytokine, and/or b) 90% or more of the mesenchymal stem cells express EGFR and/or ITGA4; and a method for producing a cell-based medicine containing mesenchymal stem cells, the method comprising the steps of: a) adding an inflammatory cytokine to a culture containing mesenchymal stem cells, and confirming that the mesenchymal stem cells express CX3CL1; and/or b) confirming that 90% or more of the mesenchymal stem cells express EGFR and/or ITGA4.

The present disclosure relates to methods for expanding and increasing the cytotoxic activity of natural killer cells comprising co-culturing, as feeder cells, a population of myeloid leukemia cells engineered to express one or more of membrane-bound IL-21 (mb IL-21) or membrane-bound IL-15 (mbIL-15) in the presence of cytokine support. The present disclosure also relates to a population of acute myeloid leukemia cells engineered to express one or more of membrane-bound IL-21 (mbIL-21) or membrane-bound IL-15 (mbIL-15). The present disclosure also relates to methods of treating cancer employing the step of expanding natural killer cells using feeder cells engineered to express one or more of membrane-bound IL-21 (mbIL-21) or membrane-bound IL-15 (mbIL-15).

The invention relates to the expansion of T cells and particularly, although not exclusively, to the expansion of gamma delta T cells, and the optimization of medium, serum and cytokine combinations for large-scale ex vivo expansion of gamma delta T cells for clinical use.

A method for producing natural killer cells is disclosed. The method comprises isolating peripheral blood mononuclear cells (PBMCs) from a blood sample; isolating at least one of CD56+ cells and/or CD3/CD56+ cells from the PBMCs; and co-culturing the at least one of CD56+ cells and/or CD3/CD56+ cells with a combination of feeder cells in the presence of a cytokine. A composition for treating cancer is also disclosed. The composition comprises the CD56+ natural killer cells produced by the disclosed method and a cytokine.

A method for producing natural killer cells is disclosed. The method comprises isolating peripheral blood mononuclear cells (PBMCs) from a blood sample; isolating at least one of CD56+ cells and/or CD3/CD56+ cells from the PBMCs; and co-culturing the at least one of CD56+ cells and/or CD3/CD56+ cells with a combination of feeder cells in the presence of a cytokine. A composition for treating cancer is also disclosed. The composition comprises the CD56+ natural killer cells produced by the disclosed method and a cytokine.

Disclosed are compositions and methods for directing NK cells to the bone marrow through the use of PM21 particles.

The present disclosure provides a method for in vitro activation of immune cells for immune cell therapies. The method includes contacting a population of immune cells with -glucan to obtain a population of conditioned cells. When introduced into a subject, the population of conditioned immune cells inhibits tumor growth in the subject. A method for inhibiting tumor growth using the population of conditioned immune cells is also provided.

Systems and methods to modulate the function of mucosal-associated invariant T (MAIT) cells in the absence of a T cell receptor (TCR) signal are described. The systems and methods can be used to elucidate the function of MAIT cells to assess potential therapeutic strategies for conditions associated with inflammation.

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.

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.