Abstract: The present invention encompasses methods for reducing the number of target cells in a subject, such as cancer cells. The methods include administration of genetically-modified human immune cells expressing a chimeric antigen receptor or exogenous T cell receptor, which have specificity for an antigen on the target cells Administration of the genetically-modified immune cells can be preceded by the administration of a lymphodepletion region and/or an immunosuppression regimen, to improve efficacy of the therapy and persistence of the cells in vivo.

Abstract: The present disclosure provides chimeric antigen receptor (CAR)-T-Rapa cells and methods of making and using them. Specifically, methods of producing T-Rapa cells that can express chimeric antigen receptors is provided.

Abstract: The present disclosure provides methods of treating lysosomal storage disorders. The method comprises producing vector-transduced T-Rapa cells that express a transgene of interest and administering the cells to a patient in need thereof.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: The present invention provides methods and compositions for converting a T cell into a cell that exhibits at least one regulatory T cell phenotype. The converted T cell is generated by contacting a T cell with a cell that is modified to comprise an agent capable of activating PD1 signaling in a T cell. The converted T cell is useful for preventing, suppressing, blocking or inhibiting an immune response. For example the converted T cell is useful for preventing rejection of a transplanted tissue in a human or other animal host, or protecting against graft versus host disease. The converted T cell can also be used to treat autoimmune diseases.

Abstract: Methods for generating highly enriched Th1/Tc1 and Th2/Tc2 functions are described. In particular, the generation of these functions are attained by the addition of an immune suppression drug, rapamycin or a rapamycin derivative compound. In addition to enhanced purity of T cell function, the T cells generated in rapamycin also express molecules that improve immune T cell function such as CD28 and CD62L. Such rapamycin generated functional T cell subsets may have application in the prevention or treatment of GVHD after allogeneic hematopoietic stem cell transplantation, the treatment of autoimmunity, or the therapy of infection or cancer.

Abstract: Methods for generating highly enriched Th1/Tc1 and Th2/Tc2 functions are described. In particular, the generation of these functions are attained by the addition of an immune suppression drug, rapamycin or a rapamycin derivative compound. In addition to enhanced purity of T cell function, the T cells generated in rapamycin also express molecules that improve immune T cell function such as CD28 and CD62L. Such rapamycin generated functional T cell subsets may have application in the prevention or treatment of GVHD after allogeneic hematopoietic stem cell transplantation, the treatment of autoimmunity, or the therapy of infection or cancer.

Abstract: The invention relates to a composition comprising a stably integrating delivery vector; and a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseases such as graft versus host disease and cancer.

Abstract: Methods for generating highly enriched Th1/Tc1 and Th2/Tc2 functions are described. In particular, the generation of these functions are attained by the addition of an immune suppression drug, rapamycin or a rapamycin derivative compound. In addition to enhanced purity of T cell function, the T cells generated in rapamycin also express molecules that improve immune T cell function such as CD28 and CD62L. Such rapamycin generated functional T cell subsets may have application in the prevention or treatment of GVHD after allogeneic hematopoietic stem cell transplantation, the treatment of autoimmunity, or the therapy of infection or cancer.

Abstract: The invention relates to a composition comprising: a stably integrating delivery vector; a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosophorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseases such as graft versus host disease and cancer.

Abstract: The invention relates to a composition comprising: a stably integrating delivery vector; a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseaseuuius such as graft versus host disease and cancer.

Abstract: Methods are provided for producing a population of substantially purified CD4+ Th1 lymphocytes. The method includes stimulating a population of substantially purified CD4+ T cells isolated from a subject by contacting the population with an anti-CD3 monoclonal antibody and an antibody that specifically binds to a T cell costimulatory molecule in the presence of a Th1 supportive environment to form a stimulated population of T cells. The stimulated population of CD4+ T cells is allowed to proliferate in a Th1 supportive environment. In one example, the Th1 supportive environment includes at least 20 IU/ml of IL-2, for example about 1000 I.U./ml of IL-2, and a neutralizing amount of an IL-4, an IL-13, and/or an IL-4/IL-13 neutralizing agent. In other examples, the supportive environment further includes at least 1 ng/ml of IL-12, for example about 2.5 ng/ml of IL-12. Purified populations of Th1 cells are disclosed herein, as are methods for their use.

Abstract: A method is provided for producing a population of substantially purified CD4+ Th2 lymphocytes. The method includes stimulating a population of substantially purified CD4+ T cells isolated from a subject by contacting the population with an immobilized anti-CD3 monoclonal antibody and an immobilized antibody that specifically binds to a T cell costimulatory molecule in the presence of a Th2 supportive environment to form a stimulated population of T cells. Purified populations of Th2 cells are disclosed herein, as are methods for their use. For example, substantially purified CD4+ Th2 lymphocytes can be used to treat graft-versus-host-disease, tumors, and autoimmune disorders.

Abstract: A method of isolating dendritic cells is described. This method involves elutriating peripheral blood samples in at least four flow rates from an elutriation rotor. Calcium ionophore is used to stimulate monocytes isolated during the process into dendritic cells. Treatments for diseases involving re-introduction of activated dentritic cells are also described.