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: 8998935
• 负责人: SCOTT R MANALIS
• 金额: $ 36.65万
• 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 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8998935
• 关键词: Acute Lymphocytic Leukemia; Address; Back; Biological Assay; Cell Line; Cells; Clinical; Clinical Research; Cytolysis; Cytotoxic Chemotherapy; Disease remission; Erythrocytes; Exhibits; Growth; Health; 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; Xenograft procedure; base; cancer cell; cantilever; cell growth; design; drug sensitivity; in vivo Model; inhibitor/antagonist; kinase inhibitor; leukemia treatment; lymphoblast; novel; prognostic value; response; scale up; sensor; 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）：我们的申请对血液癌症具有广泛的影响，但我们的具体重点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，但许多患者的深度临床反应和治愈之间的主要障碍是无法针对 MRD 进行治疗。我们提议扩大规模并验证一种新型微流体系统，该系统可以在特定治疗前后以前所未有的精度监测 MRD 样本中单个细胞的质量。该 R33 应用程序的主要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对特定疗法的生长反应是否可以预测该疗法对该患者的疗效？目前，对于持续性 MRD 患者，细胞毒治疗只是加强，而不是选择性地使用已知对特定患者最有效的治疗。我们通过直接测量细胞生长来分析 MRD 的治疗敏感性的方法将代表着利用 MRD 治疗白血病的重大进展。