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**urelumab + rituximab** is a combination of two monoclonal antibodies under investigation for B-cell lymphomas, including relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)[1][3][7]. Urelumab is a fully human IgG4 monoclonal antibody that acts as an agonist at CD137 (4-1BB), a costimulatory molecule on immune cells. By activating CD137, urelumab stimulates anti-tumor immunity, notably enhancing CD8+ T cell and natural killer (NK) cell activity, promoting their proliferation, survival, memory formation, and cytokine production, leading to cytotoxic effects against tumor cells[2]. Rituximab is a chimeric monoclonal antibody targeting CD20 on B cells, mediating B cell depletion primarily through antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity. The rationale for combining urelumab and rituximab is to potentially enhance the cytotoxic antitumor response; however, phase 1 trial results showed that the combination did not provide clinical activity beyond rituximab alone or standard care in B-cell lymphoma.
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