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A combination immunotherapy regimen consisting of the CD20-directed monoclonal antibody rituximab and recombinant human interleukin-12 (rhIL-12). Rituximab binds to the CD20 antigen on the surface of normal and malignant B-lymphocytes, mediating cell lysis through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Recombinant IL-12 is a proinflammatory cytokine that stimulates the production of interferon-gamma (IFN-γ) and enhances the activation and cytotoxic activity of natural killer (NK) cells and T-cells. The rationale for the combination is that IL-12-mediated activation of NK cells can significantly augment rituximab-induced ADCC. This combination was evaluated in Phase II clinical trials conducted by the National Cancer Institute (NCI) for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma.
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