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Recent advances have led to increasing sophistication in our ability to manipulate the immune response to prevent or treat disease. Monoclonal antibodies have emerged as a viable therapeutic approach against both cancer and autoimmune disease. Rituximab, the first monoclonal antibody approved by the FDA for cancer therapy, appears to achieve its therapeutic effects through a combination of mechanisms that may include antibody-dependent cell-mediated cytotoxicity, complement-mediated cell lysis, and the direct stimulation of apoptotic signaling pathways in target cells. Moreover, an increased understanding of the factors that govern immune tolerance has poised us on the brink of further breakthroughs in the immunotherapy of cancer and autoimmune disease. Manipulation of the signaling pathways that lead to T cell anergy may allow us to promote or overcome tolerance as appropriate in the therapy of autimmune disease and cancer. Activation of toll-like receptor pathways in dendritic cells is one approach that may help break tumor tolerance and thereby enhance the efficacy of anti-cancer dendritic cell vaccines.
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