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（应用程序提供）：我们的应用对血液学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。监测最小残留疾病（MRD）具有渐进价值的证据越来越强，但是，对于许多患者，深层临床反应与治愈之间的主要障碍是无法治疗的靶向MRD。我们提议扩大和验证一种新型的微流体系统，该系统在特定处理前后以前所未有的精度来监视MRD样品中单个细胞的质量。该R33应用的主要输送是一种可以在临床研究中使用的系统来解决以下问题：MRD在特定疗法时获得的患者癌细胞的生长反应是否预测该治疗对该患者的有效性？目前，仅针对持续MRD的患者而不是针对特定患者最有效的疗法的选择性，而不是针对持续的MRD患者的细胞毒性疗法。我们通过直接衡量细胞生长来主张MRD进行治疗敏感性的方法将代表使用MRD在治疗白血病中的显着进步。