Correlating TCR diversity to immune reconstitution after cord blood transplant

TCR 多样性与脐带血移植后免疫重建的关联

• 批准号: 8199243
• 负责人: Robert J Livingston
• 金额: $ 14.9万
• 依托单位: ADAPTIVE BIOTECHNOLOGIES CORPORATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199243
• 关键词: Adolescent; Adult; Adverse effects; Anti-Infective Agents; Biological Assay; Blood specimen; Cell Transplantation; Cell Transplants; Childhood; Clinical; Cytomegalovirus; Data; Disease; Engraftment; Ensure; Ethnic Origin; Goals; Hematologic Neoplasms; Hematopoietic; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Immune; Immune system; Immunity; Incidence; Individual; Infection; Infection prevention; Laboratories; Measurement; Measures; Methods; Minority; Morbidity - disease rate; Opportunistic Infections; Outcome; Patient Care; Patients; Phase; Predisposition; Procedures; Prophylactic treatment; Recording of previous events; Recovery; Regimen; Risk; Source; Stem cell transplant; Stem cells; T-Cell Receptor; T-Cell Receptor Genes; T-Lymphocyte; TRB@ gene cluster; Technology; Time; Transplant Recipients; Transplantation; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; Universities; Viral; Work; graft vs host disease; mortality; neutrophil; pathogen; peripheral blood; phase 1 study; prevent; reconstitution

DESCRIPTION (provided by applicant): The goal of this Phase I project is to develop a method to objectively measure immune reconstitution following hematopoietic stem cell transplantation using direct sequencing of the T-cell repertoire. This method will be developed using data from patients treated with stem cells derived from umbilical cord blood. Umbilical cord blood (CB) has emerged as an effective source of stem cells and has several advantages over conventional stem cell sources. However, cord blood recipients are at significant risk of delayed hematopoietic recovery and immune reconstitution, and thus appear to have higher susceptibility to infections, particularly from viral pathogens. The high rate of infections is associated with an alarming level of morbidity and mortality. At present, there is no objective measurement available for clinicians to determine the extent of immune reconstitution in transplant patients, and there are risks and side-effects associated with treatments currently used to prevent infections. The ability to measure immune reconstitution will relieve clinicians and their patients of the burdens associated with excessive, or insufficient, prophylactic treatments. Herein, we propose to utilize our high-throughput TCR sequencing assay to quantify the T-cell repertoire over time in individuals who have undergone cord blood transplantation. We will establish the correlation between the T-cell repertoire and reconstitution of clinical immunity. The ability to simultaneously sequence millions of individual T-cell receptor genes in single individuals provides, for the first time, the potential to directly observe changes in the immune repertoire, and this could allow clinicians to make better informed decisions about patient care. PUBLIC HEALTH RELEVANCE: The goal of this Phase I project is to develop a method to objectively measure immune reconstitution following hematopoietic stem cell transplantation using direct sequencing of the T cell repertoire. This method will be developed using umbilical cord blood transplant data, but will be relevant and beneficial to the broader transplantation field.

描述（由申请人提供）：该第一阶段项目的目标是开发一种使用 T 细胞库的直接测序来客观测量造血干细胞移植后免疫重建的方法。该方法将利用来自接受脐带血干细胞治疗的患者的数据来开发。脐带血（CB）已成为干细胞的有效来源，与传统干细胞来源相比具有多种优势。然而，脐带血接受者面临着造血恢复和免疫重建延迟的显着风险，因此似乎对感染，特别是病毒病原体的感染具有更高的易感性。高感染率与令人震惊的发病率和死亡率相关。目前，临床医生还没有客观的测量方法来确定移植患者免疫重建的程度，并且目前用于预防感染的治疗存在风险和副作用。测量免疫重建的能力将减轻临床医生及其患者与过度或不足的预防性治疗相关的负担。 在此，我们建议利用我们的高通量 TCR 测序测定来量化接受脐带血移植的个体随时间的 T 细胞库。我们将建立 T 细胞库与临床免疫重建之间的相关性。同时对单个个体中数百万个 T 细胞受体基因进行测序的能力首次提供了直接观察免疫库变化的潜力，这可以让临床医生在患者护理方面做出更明智的决策。 公共健康相关性：该第一阶段项目的目标是开发一种方法，利用 T 细胞库的直接测序来客观测量造血干细胞移植后的免疫重建。该方法将利用脐带血移植数据开发，但将与更广泛的移植领域相关并有益。