SBIR-STTR Award

Highly Sensitive Chimerism Testing to Detect Early Leukemia Relapse Post-Allo-Transplantation
Award last edited on: 10/7/2019

Sponsored Program
STTR
Awarding Agency
NIH : NCI
Total Award Amount
$299,704
Award Phase
2
Solicitation Topic Code
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Principal Investigator
Sami Barna Kanaan

Company Information

Chimerocyte Inc

2451 Perkins Lane West
Seattle, WA 98199
   (206) 432-2736
   N/A
   www.chimerocyte.tech

Research Institution

Fred Hutchinson Cancer Research Center (FHCRC)

Phase I

Contract Number: 1R41CA232805-01
Start Date: 9/21/2018    Completed: 2/28/2020
Phase I year
2018
Phase I Amount
$173,566
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.

Project Terms:
Acute; Acute leukemia; Acute Lymphocytic Leukemia; Acute Myelocytic Leukemia; Address; Alleles; Allogenic; assay development; base; Biological Assay; Blood; Bone Marrow; Cancer Diagnostics; Cells; chemotherapy; Chimerism; Clinical; clinical practice; Collaborations; Detection; Detection of Minimal Residual Disease; Diagnostics Research; Differentiation Antigens; Disease; Disease Marker; Disease remission; DNA; Dysmyelopoietic Syndromes; Early identification; Engineering; Engraftment; FDA approved; Foundations; Frequencies; Genetic; Genetic Polymorphism; Genotype; Goals; Gold; GSTT1 gene; Hematopoietic Stem Cell Transplantation; Heterogeneity; high risk; HLA Antigens; Immunotherapy; improved; In Vitro; Laboratories; Laboratory Research; Legal patent; leukemia; Malignant Neoplasms; medical attention; Methods; Microchimerism; Monitor; new technology; Outcome; Patient risk; Patients; Phase; Physicians; Polymerase Chain Reaction; Population; Predictive Value; Pregnancy; prevent; Probability; Relapse; relapse patients; relapse prediction; relapse risk; Reporting; research clinical testing; Residual Neoplasm; Resistance; Sampling; Scientist; screening; Sensitivity and Specificity; Short Tandem Repeat; Source; Specificity; standard of care; Subcategory; success; Surrogate Markers; Techniques; Technology; Testing; Therapeutic; Time; Transplantation;

Phase II

Contract Number: 5R41CA232805-02
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2019
Phase II Amount
$126,138
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.

Public Health Relevance Statement:
PROJECT NARRATIVE Increasing mixed chimerism (reemerging recipient cells) after allogeneic hematopoietic stem cell transplantation in blood malignancies correlates with relapse. Such reemerging cells can be detected early on using Chimerocyte’s technology with limits-of-detection several orders of magnitude lower than the current “gold standard” in chimerism analysis. Our technology has the potential to significantly improve early identification of patients with high risk of leukemia relapse post-transplant.

Project Terms:
Acute; Acute leukemia; Acute Lymphocytic Leukemia; Acute Myelocytic Leukemia; Address; Alleles; Allogenic; assay development; base; Biological Assay; Blood; Bone Marrow; Cancer Diagnostics; Cells; chemotherapy; Chimerism; Clinical; clinical practice; Collaborations; Detection; Detection of Minimal Residual Disease; Diagnostics Research; Differentiation Antigens; Disease; Disease Marker; Disease remission; DNA; Dysmyelopoietic Syndromes; Early identification; Engineering; Engraftment; FDA approved; Foundations; Frequencies; Genetic; Genetic Polymorphism; Genotype; Goals; Gold; Hematopoietic Stem Cell Transplantation; Heterogeneity; high risk; HLA Antigens; Immunotherapy; improved; In Vitro; Laboratories; Laboratory Research; Legal patent; leukemia; Malignant Neoplasms; medical attention; Methods; Microchimerism; Monitor; new technology; off-patent; Outcome; Patients; Phase; Physicians; Polymerase Chain Reaction; Population; post-transplant; Predictive Value; Pregnancy; prevent; Probability; Relapse; relapse patients; relapse prediction; relapse risk; Reporting; research clinical testing; Residual Neoplasm; Resistance; Sampling; Scientist; screening; Sensitivity and Specificity; Short Tandem Repeat; Source; Specificity; standard of care; Subcategory; success; Surrogate Markers; Techniques; Technology; Testing; Therapeutic; Time; Transplantation