Abstract: The present invention describes the use of leptin for the immune modulation of the Th1/Th2 response. One aspect of the invention provides for a shift in the Th1/Th2 cell balance towards pro-inflammatory cytokine producing cells. This shift results from an increase in the levels, expression and/or the activity of leptin. Another aspect of the invention provides for a shift in the Th1/Th2 cell balance towards anti-inflammatory cytokine producing cells. This shift results from a decrease in the levels, expression and/or the activity of leptin. The shifting of the Th1/Th2 balance provides a method for the treatment of a variety of diseases and disorders.

Abstract: The present invention relates to methods for the modulation of immune responses. More particularly, the invention relates to methods and uses of leptin for immune-modulation of the balance between the Th1/Th2 responses and for the treatment of immune-related disorders. Specifically, the methods of the invention comprise shifting the Th1/Th2 cell balance towards the proinflammatory state. This modulation of the cell balance may be performed by increasing the activity and/or the expression of leptin in a subject, for instance by raising the amount of leptin. The amount of leptin in a subject may be increased by activating immunoregulatory cells, or by administering an immunomodulatory amount of leptin or a homologue, derivative, or functional fragment of leptin.

Abstract: The present invention relates to methods for the modulation of immune responses. More particularly, the invention relates to methods and uses of leptin for immuno-modulation of the balance between the Th1/Th2 responses and for the treatment of immune-related disorders. Specifically, the methods of the invention comprise shifting the Th1/Th2 cell balance towards the proinflammatory state. This modulation of the cell balance may be performed by increasing the activity and/or the expression of leptin in said subject, for instance by raising the amount of leptin. The amount of leptin in a subject may be increased by activating immunoregulatory cells, administering an immunomodulatory amount of leptin or a homologue, derivative, or functional fragment of leptin.

Abstract: A redirected Treg cell is endowed with specificity toward a selected target antigen or ligand. The cell contains a chimeric receptor polypeptide that is expressed in a single, continuous chain, with an extracellular recognition region displayed on the surface of the cell, a transmembrane region and an intracellular signaling region. The extracellular recognition region is specific for the selected target antigen or ligand. The intracellular signaling region includes a combination of T-cell signaling polypeptide moieties, which combination, upon binding of the extracellular recognition region to the selected target antigen or ligand, triggers activation of the redirected Treg cells to cause suppression of T-cell mediated immunity. Such redirected Treg cells may be used to suppress undesired activity of T effector cells thereby mediating an immune or inflammatory response.

Abstract: The present invention describes the use of leptin for the immune modulation of the Th1/Th2 response. One aspect of the invention provides for a shift in the Th1/Th2 cell balance towards pro-inflammatory cytokine producing cells. This shift results from an increase in the levels, expression and/or the activity of leptin. Another aspect of the invention provides for a shift in the Th1/Th2 cell balance towards anti-inflammatory cytokine producing cells. This shift results from a decrease in the levels, expression and/or the activity of leptin. The shifting of the Th1/Th2 balance provides a method for the treatment of a variety of diseases and disorders.

Abstract: Leptin was previously demonstrated to exert potent immune modulatory properties in several immune mediated disorders. The aim of the study was to determine leptin's anti-tumor effect in a murine model of human hepatocellular carcinoma (HCC). In vivo, Athymic T cell deficient (nude) mice transplanted with 1×106 human Hep3B cells, followed by administration of two daily intraperitoneal doses of 0.5 mg/gram leptin for 6 weeks. Leptin administration induced a significant reduction in tumor size and improved survival in nude mice. Histologically, tumors of leptin-administered mice featured increased inflammatory exudate in interphase areas. Leptin-induced tumor suppression was associated with a significant increase in peripheral natural killer (NK) cell number. Splenocytes from leptin-treated mice featured decreased expression of CIS mRNA.

Abstract: The present invention relates to a method for the treatment of immune-related or immune-mediated disorders in a mammalian subject in need of such treatment. This method comprises the step of manipulating the NKT cell population in said subject by suitable means, said manipulation of the NKT cell population resulting in modulation of the Th1/Th2 balance toward anti-inflammatory cytokine producing cells. Manipulation of the NKT cell population may be performed either by depletion of said cells by a suitable means or alternatively by ex vivo education of the NKT cells, such that the educated NKT cells have the capability to modulate the Th1/Th2 balance toward anti-inflammatory cytokine producing cells. The invention further relates to pharmaceutical compositions for the treatment of immune-related or immune-mediated disorders in a mammalian subject. These compositions comprising as an effective ingredient an ex vivo educated NKT cell.

Abstract: The present invention relates to a method for the treatment of immune-related disorders in a mammalian subject in need of such treatment. This method comprises the step of manipulating the NK T cell population in said subject by suitable means, said manipulation of the NK T cell population resulting in modulation of the Th1/Th2 balance toward anti-inflammatory cytokine producing cells. Manipulation of the NK T cell population may be performed either by depletion of said cells by a suitable means or alternatively by ex vivo education of the NK T cells, such that the educated NK T cells have the capability to modulate the Th1/Th2 balance toward anti-inflammatory cytokine producing cells.