Correlating TCR diversity to immune reconstitution after cord blood transplant

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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.