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N-803 + rituximab is a combination immunotherapy consisting of N-803—a novel interleukin-15 (IL-15) receptor superagonist complex—and rituximab, an anti-CD20 monoclonal antibody. N-803 is engineered to enhance the in vivo persistence and trans-presentation of IL-15, leading to potent activation and proliferation of natural killer (NK) cells and CD8+ T cells. Rituximab targets CD20-positive B cells and mediates antibody-dependent cellular cytotoxicity (ADCC). Combined, these agents synergize: N-803 augments the effector function of NK and CD8+ T cells, enhancing rituximab-driven tumor targeting and immune-mediated killing of malignant B-cells. This regimen has been evaluated in relapsed/refractory indolent non-Hodgkin lymphoma (iNHL), demonstrating robust expansion of NK and CD8+ T-cell populations, immune activation, remodeling of monocyte transcriptional programs, and encouraging response rates—even in rituximab-refractory patients[1][3][4][5].
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