CELL INTELLIGENCE · 肿瘤细胞治疗研究

Natural killer (NK) cell dysfunction contributes to tumor resistance, particularly in antibody-dependent cell-mediated cytotoxicity. This study evaluated a fully chemically defined system for expanding high-purity NK (hpNK) cells and their clinical application. In preclinical studies, hpNK demonstrated strong antibody-dependent cell-mediated cytotoxicity activity in combination with rituximab. An exploratory clinical trial involving 19 patients with relapsed/refractory diffuse large B-cell lymphoma assessed the safety and preliminary clinical efficacy of combining allogeneic hpNK (shiheleucel) with anti-CD20 antibody and chemotherapy. Among 17 patients treated, no dose-limiting toxicity was observed. Among the 12 patients who underwent at least 1 postbaseline positron emission tomography and computed tomography efficacy assessment, the investigator-assessed objective response rate was 75.0% (9/12), including 7 complete responses and 2 partial responses. Median progression-free survival was 24 weeks, with median overall survival not reached at the time of analysis. Shiheleucel demonstrated a manageable safety profile and preliminary clinical activity, warranting further evaluation in larger controlled studies. SIGNIFICANCE STATEMENT: This study demonstrates that a fully chemically defined expansion system can generate high-purity natural killer (NK) cells with potent antibody-dependent cell-mediated cytotoxicity activity in preclinical settings. In an exploratory clinical trial combining allogeneic NK cell therapy with anti-CD20 antibody and chemotherapy to treat relapsed/refractory diffuse large B-cell lymphoma provided a manageable safety profile and evidence of clinical activity. These findings support further investigation of antibody-dependent cell-mediated cytotoxicity-driven NK cell-based allogeneic cell therapy.