Institute of Anesthesiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland.
Int J Mol Sci. 2023 Apr 19;24(8):7523. doi: 10.3390/ijms24087523.
In the past, our research group was able to successfully remove circulating tumor cells with magnetic nanoparticles. While these cancer cells are typically present in low numbers, we hypothesized that magnetic nanoparticles, besides catching single cells, are also capable of eliminating a large number of tumor cells from the blood ex vivo. This approach was tested in a small pilot study in blood samples of patients suffering from chronic lymphocytic leukemia (CLL), a mature B-cell neoplasm. Cluster of differentiation (CD) 52 is a ubiquitously expressed surface antigen on mature lymphocytes. Alemtuzumab (MabCampath) is a humanized, IgG1κ, monoclonal antibody directed against CD52, which was formerly clinically approved for treating chronic lymphocytic leukemia (CLL) and therefore regarded as an ideal candidate for further tests to develop new treatment options. Alemtuzumab was bound onto carbon-coated cobalt nanoparticles. The particles were added to blood samples of CLL patients and finally removed, ideally with bound B lymphocytes, using a magnetic column. Flow cytometry quantified lymphocyte counts before, after the first, and after the second flow across the column. A mixed effects analysis was performed to evaluate removal efficiency. < 0.05 was defined as significant. In the first patient cohort ( = 10), using a fixed nanoparticle concentration, CD19-positive B lymphocytes were reduced by 38% and by 53% after the first and the second purification steps ( = 0.002 and = 0.005), respectively. In a second patient cohort ( = 11), the nanoparticle concentration was increased, and CD19-positive B lymphocytes were reduced by 44% ( < 0.001) with no further removal after the second purification step. In patients with a high lymphocyte count (>20 G/L), an improved efficiency of approximately 20% was observed using higher nanoparticle concentrations. A 40 to 50% reduction of B lymphocyte count using alemtuzumab-coupled carbon-coated cobalt nanoparticles is feasible, also in patients with a high lymphocyte count. A second purification step did not further increase removal. This proof-of-concept study demonstrates that such particles allow for the targeted extraction of larger amounts of cellular blood components and might offer new treatment options in the far future.
过去，我们的研究小组成功地使用磁性纳米粒子清除了循环肿瘤细胞。虽然这些癌细胞通常数量较少，但我们假设，除了捕获单个细胞外，磁性纳米粒子还能够从血液中外在去除大量肿瘤细胞。在一项针对患有慢性淋巴细胞白血病 (CLL) 的患者的小型初步研究中，我们测试了这种方法，CLL 是一种成熟的 B 细胞肿瘤。分化群（CD）52 是成熟淋巴细胞上普遍表达的表面抗原。阿仑单抗（MabCampath）是一种针对 CD52 的人源化 IgG1κ 单克隆抗体，以前临床上批准用于治疗慢性淋巴细胞白血病 (CLL)，因此被认为是进一步测试开发新治疗方案的理想候选药物。阿仑单抗与碳包覆钴纳米粒子结合。将粒子添加到 CLL 患者的血液样本中，最后使用磁性柱理想地去除与结合的 B 淋巴细胞。流式细胞术在使用柱子之前、第一次和第二次通过后定量淋巴细胞计数。进行混合效应分析以评估去除效率。 < 0.05 被定义为显著。在第一个患者队列（= 10）中，使用固定的纳米粒子浓度，CD19 阳性 B 淋巴细胞在第一次和第二次纯化步骤后分别减少了 38%和 53%（= 0.002 和= 0.005）。在第二个患者队列（= 11）中，增加了纳米粒子浓度，CD19 阳性 B 淋巴细胞减少了 44%（< 0.001），第二次纯化后没有进一步去除。在淋巴细胞计数较高 (>20 G/L) 的患者中，使用较高的纳米粒子浓度可观察到效率提高约 20%。使用阿仑单抗偶联碳包覆钴纳米粒子，B 淋巴细胞计数可减少 40%至 50%，在淋巴细胞计数较高的患者中也是如此。第二次纯化步骤不会进一步增加去除效果。这项概念验证研究表明，这种粒子允许有针对性地提取更多数量的血液细胞成分，并可能在不久的将来提供新的治疗选择。
