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Correlating TCR diversity to immune reconstitution after cord blood transplant

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2013 / SBIR
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-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2013
Title: Correlating TCR diversity to immune reconstitution after cord blood transplant
Agency: HHS
Contract: 2R44HL106868-02
Award Amount: $2,528,467.00
 

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.

Principal Investigator:

Mark J. Rieder
206-659-0067
mrieder@adaptivebiotech.com

Business Contact:

Caterina Bertucci
206-436-6357
cbertucci@adaptivebiotech.com
Small Business Information at Submission:

ADAPTIVE TCR CORPORATION
1551 Eastlake Avenue East Suite 200 SEATTLE, WA 98102-

EIN/Tax ID: 127090702
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No