The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TOR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×10.sup.5 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoietic cells are obtained by separating the T cells from the immature hematopoietic cells by magnetic cell sorting, and (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per body weight, thereby treating the subject.

The invention provides methods of isolating CD127.sup.lo/− immunosuppressive regulatory T cells which can be greatly enriched for FoxP3, methods of expanding the isolated cells, pharmaceutical compositions of such cells, and methods of their use in the treatment of autoimmune and other immune system mediated disorders.

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Multispecific molecules that include i) a tumor-targeting moiety; and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager); (iii) a cytokine molecule; and/or (iv) a stromal modifying moiety are disclosed. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors comprise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

The inventors have developed a metastatic 4T1 breast tumor model in BALB/c mice. They have shown that the vaccination with xenogeneic embryonic stem cells in combination with valproic acid (VPA) generates a higher anti-tumoral response against breast cancer and inhibits metastasis development. They established that these responses are achieved only by the addition of valproic acid in the therapeutic regimen in comparison to the use ESCs or iPSCs alone. Thus, the inventors provide a new therapeutic strategy to treat cancers expressing embryonic antigens. Accordingly, the present invention relates to i) a population of pluripotent cells and ii) a compound selected from a group which activates MHC expression, as a combined preparation for use in a method for treating a subject suffering from a cancer, comprising a step of administering simultaneously, separately or sequentially to said subject a therapeutically amount thereof.

The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. In one embodiment, the invention provides a universal immune receptor that comprises a protein or peptide tag, such as a SpyCatcher or a SpyTag moiety, bound to an extracellular hinge region, a transmembrane domain, and an intracellular domain for T cell activation.

Chordoma is treated in a patient by co-administration of an anti-EGFR antibody and high affinity NK cells (haNK). Most preferably, the antibody is non-covalently bound to a high affinity variant of a CD16 receptor or administered before transfusion of the haNK cells to so target the chordoma cells for cytotoxic cell killing by the haNK cells.