1R41CA232805-01 (R41) ApplID: 9619598 | |||
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Title | Highly Sensitive Chimerism Testing to Detect Early Leukemia Relapse Post-Allo-Transplantation | ||
Institution | CHIMEROCYTE, INC., SEATTLE, WA | ||
Principal Investigator | KANAAN, SAMI | NCI Program Director | Hallett |
Cancer Activity | Small Business - Cancer Detection/ Diagnosis/ Prog | Division | SBIRDC |
Funded Amount | $173,566 | Project Dates | 09/21/2018 - 02/28/2020 |
Fiscal Year | 2018 | Project Type | Grant |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Bone Marrow Transplantation (100.0%) Childhood Cancers (50.0%) Chronic Myeloproliferative Disorders (50.0%) Organ Transplantation Research (100.0%) |
Childhood Leukemia (50.0%) Leukemia (100.0%) |
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Research Type | |||
Technology Development and/or Marker Discovery Systemic Therapies - Discovery and Development |
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Abstract | |||
ABST RACT Patients with acute blood malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT) are monitored for minimal residual disease (MRD) as predictive of relapse. Increasing mixed chimerism (reemerging recipient cells) correlates with reappearance of underlying disease by association with MRD. Genetic and immunophenotypic heterogeneity of these malignancies often prevents establishing reliable MRD markers, in which case donor-vs.-recipient chimerism testing becomes the best option as a surrogate marker for MRD. At present, the widely used ?gold standard? in chimerism analysis is techniques characterizing short tandem repeats (STR) with a limit-of-detection ? 1:100, thus unsuitable as a strategy for early relapse detection. New technologies to predict relapse post-HSCT are critical to provide rapid and individualized therapeutic assessment. Chimerocyte, Inc. is developing the Microchimerism Panel, composed of polymorphism-specific primers and fluorogenic probes to detect and quantify non-shared polymorphisms with limit-of-detection several orders of magnitude lower than currently available tests, detecting up to 1 cell equivalent per 105 background cells. To increase the probability of having an informative marker, Chimerocyte aims at developing additional highly-sensitive polymorphism-specific assays thus expanding the panel. Furthermore, we hypothesize that by sensitively monitoring chimerism using our technology, imminent relapse will be predicted with superior accuracy compared to clinical standard-of-care. We propose to test the Microchimerism Panel on post-transplant samples from 180 leukemia patients for its ability to differentiate relapse vs. sustained remission. Our collaborators have previously collected samples from regular intervals post-transplant. Results will be compared to clinical standard- of-care chimerism testing to demonstrate the ability of Chimerocyte?s Microchimerism panel in rapid high-risk patient identification. We anticipate a successful outcome that will significantly benefit cancer diagnostics and ther apy." |