Correlating TCR diversity to immune reconstitution after cord blood transplant

描述（由申请人提供）：该I期项目的目标是开发一种方法，使用T细胞库的直接测序客观地测量造血干细胞移植后的免疫重建。这种方法将使用来自脐带血干细胞治疗患者的数据进行开发。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几个优势。然而，脐带血受者存在造血恢复和免疫重建延迟的显著风险，因此似乎对感染，特别是来自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有关。目前，临床医生还没有客观的测量方法来确定移植患者的免疫重建程度，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测序分析，以量化T细胞库随着时间的推移，在个人谁经历了脐带血移植。我们将建立T细胞库和临床免疫重建之间的相关性。在单个个体中同时测序数百万个单个T细胞受体基因的能力首次提供了直接观察免疫库变化的可能性，这可以使临床医生对患者护理做出更明智的决定。 公共卫生相关性：该I期项目的目标是开发一种方法，使用T细胞库的直接测序来客观地测量造血干细胞移植后的免疫重建。这种方法将使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。

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.