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(申请人提供)：我们的申请对血液学癌症有广泛的影响，但我们的重点将放在急性淋巴母细胞白血病上。越来越多的证据表明，监测微小残留病(MRD)具有预后价值，然而，许多患者在深度临床反应和治愈之间的主要障碍一直是无法在治疗上针对MRD。我们建议扩大和验证一种新的微流控系统，该系统在提供特定治疗之前和之后以前所未有的精度监测MRD样本中单个细胞的质量。这个R33应用程序的主要成果是一个可用于临床研究的系统，用于解决以下问题：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，细胞毒治疗只是对持续性MRD患者进行强化，而不是选择性地针对特定患者进行已知最有效的治疗。我们通过直接测量细胞生长来检测MRD的治疗敏感性的方法将代表着在白血病治疗中利用MRD的存在的重大进展。