Josefine Krüger , Igor Wolfgang Blau , Olga Blau , Alice Bettelli , Laura Rocchi , Massimo Bocchi , Jan Krönke , Lars Bullinger , Ulrich Keller , Axel Nogai
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引用次数: 0
摘要
多发性骨髓瘤是一种浆细胞侵袭性肿瘤。虽然许多药物已获得批准,但缺乏针对个体药物反应的既定预测指标构成了挑战。在这项研究中,我们探索了基于微波和荧光的 Cellply CC-Array® 技术,该技术可用于体外药物反应的高通量分析,是患者治疗效果的潜在预测标志物。此外,我们还研究了该技术在评估效应细胞有效性方面的应用。我们从 22 名患者的骨髓中分离出单核细胞,分析了原发性骨髓瘤细胞的体外药物反应。原代患者样本对美法仑、硼替佐米和地塞米松的体外反应与患者的临床反应相关。由于骨髓瘤体外存活率低导致培养时间有限,这种方法在确定对来那度胺、达拉曲单抗和艾洛妥珠单抗的敏感性方面存在局限性。通过分析细胞接近性,该平台能够评估 NK 和 T 细胞的个体抗肿瘤活性。总之,CC-Array 微阵列技术可以在体外评估骨髓瘤细胞对用于多发性骨髓瘤治疗的特定药物的反应。为了进一步验证这些体外结果与体内结果的一致性,有必要对更大的群体进行筛选。
In vitro testing of drug response in primary multiple myeloma cells using a microwell-based technology
Multiple myeloma is an aggressive neoplasm of plasma cells. While numerous drugs have gained approval, the absence of established predictive markers for individual drug responses poses a challenge. In this study, we explored the microwell- and fluorescence-based Cellply CC-Array® technology for high-throughput analysis of in vitro drug responses as a potential predictive marker for patient treatment outcomes. Furthermore, we investigated its application for evaluating effector cell effectiveness. Mononuclear cells were isolated from the bone marrow of 22 patients, and in vitro drug response of primary myeloma cells was analyzed. In vitro responses towards melphalan, bortezomib, and dexamethasone in primary patient samples correlated with clinical response of the patients. The approach exhibited limitations in identifying sensitivity towards lenalidomide, daratumumab, and elotuzumab due to limited culturing time caused by poor myeloma viability in vitro. Through the analysis of cell proximity, the platform enabled the assessment of individual anti-tumor activity from NK and T cells. In summary, the CC-Array microwell technology allowed assessment of myeloma cell responses to selected drugs used in multiple myeloma therapy in vitro. To further validate these in vitro results against in vivo outcomes, screening a larger cohort is necessary.
期刊介绍:
Leukemia Research an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. The editors encourage the submission of articles relevant to hematological malignancies. The Journal scope includes reporting studies of cellular and molecular biology, genetics, immunology, epidemiology, clinical evaluation, and therapy of these diseases.