中文摘要
多发性骨髓瘤是一种侵袭性浆细胞肿瘤。尽管已有众多药物获批,但缺乏针对个体药物反应的既定预测标志物仍构成挑战。在本研究中,我们探索了基于微孔和荧光的 Cellply CC-Array® 技术,用于高通量分析体外药物反应,作为患者治疗结局的潜在预测标志物。
此外,我们研究了其在评估效应细胞有效性方面的应用。从 22 例患者的骨髓中分离单核细胞,并分析原代骨髓瘤细胞的体外药物反应。原代患者样本对 melphalan、bortezomib 和 dexamethasone 的体外反应与患者的临床反应相关。由于骨髓瘤在体外活力差导致培养时间有限,该方法在识别对 lenalidomide、daratumumab 和 elotuzumab 的敏感性方面表现出局限性。通过分析细胞邻近关系,该平台能够评估 NK 和 T 细胞的个体抗肿瘤活性。
总之,CC-Array 微孔技术允许在体外评估骨髓瘤细胞对多发性骨髓瘤治疗中所选用药物的反应。为了进一步验证这些体外结果与体内结局的一致性,需要筛选更大的队列。
展开英文摘要原文
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.
论文信息
- 作者
- Krüger J、Blau IW、Blau O、Bettelli A、Rocchi L、Bocchi M、Krönke J、Bullinger L
- 单位
- Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 12203, Germany. Electronic address: josefine.krueger@charite.de.Germany
- 文献类型
- 非美国政府资助研究
- 期刊
- Leukemia research2024 Dec