Uses of bispecific antibody coated dendritic cells pulsed with antigens and gm-csf in immune regulation

A method to induce antigen specific T-cell tolerance for treating an autoimmune disease, the method comprising:

• (a) contacting a dendritic cell with GM-CSF to obtain a semi-mature dendritic cell;
• (b) pulsing the semi-mature dendritic cell with an antigen of interest;
• (c) coating the pulsed semi-mature dendritic cell with a bispecific antibody capable of binding a T-cell receptor on an activated T-cell;
• and
• (d) modulating the production of a regulatory T-cell to induce T-cell tolerance.

A method to treat a T and B cell mediated autoimmune disease and reduce the risk of a graft rejection by the host in a mammal, the method comprising:

• (a) presenting an antigen responsible for the autoimmune disease or the graft rejection by the host to a dendritic cell;
• (b) culturing bispecific antibody coated dendritic cells with a population of T-cells to induce antigen specific T-cell tolerance, wherein the bispecific antibody is capable of binding to a dendritic cell associated with the antigen and also with a T-cell through a T-cell receptor;
• and
• (c) administering the population of T-cells to the host and the bispecific antibody coated antigen bound dendritic cells to treat the autoimmune disease and to reduce the graft rejection.

A method to affect maturation of dendritic cells, wherein the cells are held in semi-mature status that can induce regulatory T cells, the method comprising

• (a) pulsing dendritic cells;
• (b) contacting the dendritic cells with GM-CSF;
• and
• (c) coating the pulsed dendritic cells with an appropriate bi-specific antibody, wherein one arm provides target or antigen specificity and the other arm provides CTLA-4 ligation.

A method to treat a T- and B-cell mediated autoimmune disease and prevent allograft rejection, the method comprising:

• (a) treating dendritic cells with GM-CSF to maintain the dendritic cells in a semi-mature state in the presence of an antigen of interest, wherein the antigen is an alloantigen or an autoantigen;
• (b) inducing the semi-mature dendritic cells in vitro or in vivo;
• (c) using semi-mature dendritic cells either in vivo or in vitro as antigen presenting cells to induce regulatory T-cells capable of producing IL-10 and/or TGF-beta to suppress effector T cell functions;
• and
• (d) treating the autoimmune disease with the regulatory T cells, wherein the regulatory T cells are induced in vivo with GM-CSF followed by a treatment with a bi-specific antibody to suppress T-cell function.

A method of treating an autoimmune disease comprising administering to a patient in need of treatment, a therapeutically effective amount of a composition comprising antigen-activated semi-mature dendritic cells, wherein the dendritic cells are produced by a method comprising culturing a tissue source in a culture medium, comprising GM-CSF and at least one other factor selected from the group consisting of IL-10, IL-4 or TGFβ, which inhibits proliferation or maturation of non-dendritic cell precursors, thereby increasing the proportion of dendritic cell precursors in the culture;

• wherein the dendritic cells are pulsed with a self-protein or alloantigen, and wherein the dendritic cells process the self-protein to produce a modified self-protein antigen or alloantigen, which is expressed by the dendritic cells;
• coating the semi-mature antigen bearing dendritic cells with a bi-specific antibody that is capable of binding to a dendritic cell associated with an antigen and also with a T-cell through a T-cell receptors;
• and
• administering the semi-mature dendritic cells into the host.