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TAK-981 + rituximab is a combination therapy being investigated for the treatment of relapsed or refractory CD20-positive non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. **TAK-981** (also known as subasumstat) is a first-in-class small molecule inhibitor of the SUMOylation pathway, which is involved in the regulation of many cellular processes such as DNA repair, cell cycle, and immune response. By inhibiting the SUMO-activating enzyme, TAK-981 promotes activation of type I interferon signaling and enhances antitumor immune responses, particularly augmenting the effectiveness of therapeutic antibodies by increasing antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). **Rituximab** is a monoclonal antibody targeting CD20 on B cells and mediates B-cell depletion via immune effector mechanisms. The combination of TAK-981 and rituximab exploits both direct antitumor effects and the potentiation of immune-mediated clearance of tumor cells by enhancing the function of myeloid cells and NK cells. The combination is under clinical investigation for hematologic malignancies[1][2][3][5][6].
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