Single cell growth assay for residual cells in acute lymphoblastic leukemia

急性淋巴细胞白血病残留细胞的单细胞生长测定

• 批准号: 9253358
• 负责人: SCOTT R MANALIS
• 金额: $ 45.05万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9253358
• 关键词: Acute Lymphocytic Leukemia; Address; Alpha Cell; Back; Biological Assay; Cancer Patient; Cell Line; Cells; Clinical; Clinical Research; Cytolysis; Cytotoxic Chemotherapy; Disease remission; Erythrocytes; Exhibits; Growth; Hematologic Neoplasms; Heterogeneity; Hour; Human; In Situ; Individual; Measures; Microfluidic Microchips; Microfluidics; Monitor; Morphologic artifacts; Mus; Optics; Patients; Phenotype; Population; Prior Therapy; Procedures; Residual Neoplasm; Residual state; Resistance; Sampling; Series; Sorting - Cell Movement; Spleen; System; Technology; Therapeutic; Time; Treatment Efficacy; base; cancer cell; cantilever; cell growth; design; drug sensitivity; in vivo Model; inhibitor/antagonist; kinase inhibitor; leukemia treatment; lymphoblast; novel; prognostic value; public health relevance; response; scale up; sensor; therapeutic target; tumor heterogeneity

 DESCRIPTION (provided by applicant): Our application has broad implications for hematologic cancers but our specific focus will be on acute lymphoblastic leukemias. Evidence that monitoring minimal residual disease (MRD) has prognostic value is becoming increasingly strong, however the primary roadblock between deep clinical response and cure for many patients has been the inability to therapeutically target MRD. We are proposing to scale-up and validate a novel microfluidic system that monitors the mass of individual cells within an MRD sample with unprecedented precision before and after delivery of a particular treatment. The primary deliverable of this R33 application is a system that can be used in clinical studies to address the following question: Does the growth response of a patient's cancer cells obtained at the time of MRD to a particular therapy predict that therapy's efficacy for that patient? At present, cytotoxic therapy is simply intensified for patients with persistent MRD, rather than selectivity targeting it with a therapy known to be most effective for a particular patient. Our approach of assaying MRD for therapeutic sensitivity by a direct measure of cell growth would represent a significant advance in utilizing the presence of MRD in the treatment of leukemia.

 描述（由申请人提供）：我们的应用对血液癌症具有广泛的影响，但我们的具体重点将是急性淋巴细胞白血病。监测微小残留病（MRD）具有预后价值的证据越来越多，但深度临床反应之间的主要障碍。许多患者的治疗方法是无法针对 MRD 进行治疗。我们建议扩大并验证一种新型微流体系统，该系统可以前所未有地监测 MRD 样本中的单个细胞质量。该 R33 应用程序的主要交付成果是一个可用于临床研究的系统，以解决以下问题：在 MRD 时获得的患者癌细胞的生长反应是否对特定治疗有反应。目前，细胞毒性治疗只是针对持续性 MRD 患者进行强化治疗，而不是选择性地使用已知对特定患者最有效的治疗方法来检测 MRD 的治疗敏感性。通过直接细胞生长的测量将代表利用 MRD 治疗白血病的重大进展。