USC Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy.
Blood. 2011 Jan 13;117(2):510-8. doi: 10.1182/blood-2010-06-290858. Epub 2010 Nov 3.
We have investigated combining adoptive immunotherapy with cytokine-induced killer (CIK) cells and anti-CD20 monoclonal antibodies (mAb) GA101 or rituximab to optimize B-cell non-Hodgkin lymphoma (B-NHL) therapy. CIK cultures alone demonstrated significant cytotoxic activity against B-NHL cell lines or freshly isolated samples in either an autologous or allogeneic combination. This natural cytotoxicity (NC) was mainly due to the predominating CD3(+)CD56(+) CIK population (40%-75%) present in the cultures. The addition of anti-CD20 mAb GA101 or rituximab further increased cytotoxicity by 35% and 15%, respectively. This enhancement was mainly due to antibody-dependent cytotoxicity (ADCC) mediated by the 1%-10% NK cells contaminating CIK cultures. The addition of human serum (HS) inhibited NK-cell activation induced by rituximab, but not activation induced by GA101.Overall lysis in presence of serum, even of a resistant B-NHL cell line, was significantly increased by 100 μg/mL of rituximab, but even more so by GA101, with respect to CIK cultures alone. This was due to the combined action of complement-mediated cytotoxicity (CDC), ADCC, and CIK-mediated NC. These data suggest that rituximab, and even more so GA101, could be used in vivo to enhance CIK therapeutic activity in B-NHL.
我们研究了过继免疫疗法与细胞因子诱导的杀伤（CIK）细胞和抗 CD20 单克隆抗体（mAb）GA101 或利妥昔单抗联合应用，以优化 B 细胞非霍奇金淋巴瘤（B-NHL）的治疗。CIK 培养物单独在自体或同种异体组合中对 B-NHL 细胞系或新鲜分离的样本显示出显著的细胞毒性活性。这种自然细胞毒性（NC）主要归因于培养物中占主导地位的 CD3(+)CD56(+)CIK 群体（40%-75%）。添加抗 CD20 mAb GA101 或利妥昔单抗可分别使细胞毒性增加 35%和 15%。这种增强主要是由于 1%-10%的 NK 细胞污染 CIK 培养物，通过抗体依赖性细胞毒性（ADCC）介导。人血清（HS）的添加抑制了利妥昔单抗诱导的 NK 细胞激活，但不抑制 GA101 诱导的激活。即使在存在耐药 B-NHL 细胞系的情况下，添加血清后总溶解率也显著增加，添加 100μg/mL 的利妥昔单抗可增加 100μg/mL，而添加 GA101 则可增加更多，相对于单独的 CIK 培养物。这是由于补体介导的细胞毒性（CDC）、ADCC 和 CIK 介导的 NC 的共同作用。这些数据表明，利妥昔单抗，甚至更 GA101，可在体内用于增强 CIK 在 B-NHL 中的治疗活性。
