Correlating TCR diversity to immune reconstitution after cord blood transplant

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$2,528,467.00
Award Year:
2013
Program:
SBIR
Phase:
Phase II
Contract:
2R44HL106868-02
Agency Tracking Number:
R44HL106868
Solicitation Year:
2013
Solicitation Topic Code:
NHLBI
Solicitation Number:
PA12-088
Small Business Information
ADAPTIVE TCR CORPORATION
1551 Eastlake Avenue East, Suite 200, SEATTLE, WA, 98102-
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
832591544
Principal Investigator:
MARK RIEDER
(206) 659-0067
mrieder@adaptivebiotech.com
Business Contact:
CATERINA BERTUCCI
(206) 436-6357
cbertucci@adaptivebiotech.com
Research Institution:
Stub




Abstract
DESCRIPTION (provided by applicant): Many patients requiring stem cell transplantation for hematological malignancies are unable to find a suitable HLA-matched sibling or unrelated donor. Transplants using stem cells from umbilical cord blood provide an alternative for these patients, allowing transplantation to proceed with less stringent HLA-matching requirements. Unfortunately, in addition to the risk of relapsed disease, patients undergoing cord blood transplants have a high risk of death from infections due to slow reconstitution of their immune system. In this clinical observational study, we propose to use high-throughput DNA sequencing of T- Cell Receptor (TCR) and Immunoglobulin heavy chain (IgH) genes from peripheral blood to study the reconstitution of the adaptive immune system following cord blood transplant. We will use high-throughput sequencing to estimate the diversity of T- and B-cell receptors in each of approximately 240 patients at defined time-points following transplant, and demonstrate a correlation between our measure of adaptive immune receptor diversity and subsequent morbidity and mortality from infectious complications. Further development of this technique would lead to a Phase III application with a clinical interventionstudy in which this assay would provide a diagnostic method to identify patients at high risk for infectious complications soon after transplant. Clinical care would be administered for an increased-intensity regimen of antimicrobial prophylaxis to high-risk patients. We expect that early identification of high-risk patients, combined with more aggressive prophylaxis for these patients, will reduce the high treatment-related mortality present in cord blood transplants. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The goal of this Phase II SBIR submission is to evaluate the ability of high-throughput T- and B- Cell Receptor sequencing to predict the risk of infectious complications in patients recovering from umbilical cord blood-derived stem cell transplants. Such transplants carry a high risk of patient mortality, but if successful this study will lead to improved management of infectious disease based on each patient's individual risk and improved overall patient survival.

* information listed above is at the time of submission.

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