Rapid Testing of Drug Resistant BCR-ABL(+) Leukemia Cells

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44CA153614-02
Agency Tracking Number: R44CA153614
Amount: $1,020,897.00
Phase: Phase II
Program: SBIR
Awards Year: 2013
Solicitation Year: 2013
Solicitation Topic Code: NCI
Solicitation Number: PA12-088
Small Business Information
4 ARROW DR, WOBURN, MA, 01801-2040
DUNS: 122648533
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (781) 933-3635
Business Contact
Phone: (781) 933-3635
Email: rieder@biosensetech.com
Research Institution
DESCRIPTION (provided by applicant): Resistance to chemotherapeutic drugs is an ongoing problem that results in eventual treatment failures or suboptimal patient outcomes. Approximately one-quarter of BCR-ABL(+) leukemia patients demonstrate evidence of resistance to imatinib mesylate either at initial diagnosis or at some point after treatment has begun. In our Phase I investigation, we demonstrated that monitoring the cellular stress developed by BCR-ABL(+) leukemia cells in response to tyrosine kinase inhibiting (TKI) drugs can used as an early marker for determining the effect of the therapeutic agents on the cancer cells. The approach is optimally implemented by measuring the dielectric permittivity of drug-treated cell suspensions using differential impedance sensing. Corresponding measurements of drug-sensitive and drug-resistant BCR-ABL(+) cell lines were obtained and confirmed by MTT assay. The response of non-leukemic peripheral blood mononuclear cells (PBMCs) to TKIs measured at clinically relevantdrug concentrations showed no significant background level. Finally, the responses of BCR-ABL(+) patient blood to different TKIs were consistent with our initial cell line measurements laying the foundation for a practical clinical assay. In this Phase Ieffort we propose to quantify the cellular stress related drug responses enabling ease in interpretation of results, develop prototype instrumentation, verify the technical approach through animal model measurements and demonstrate feasibility with patientsamples. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The development of a rapid diagnostic tool for determining the sensitivity/resistance profiles of leukemia cells to therapeutic agents is a significant step towards the administration ofpersonalized medicine and optimal patient outcomes. By addressing and overcoming a significant technical barrier (the ability to determine the effects of a therapeutic agent on difficult to culture cancer cells), the proposed project enables drug-resistant cancer cells to be distinguished from drug-sensitive cells easily and rapidly. The availability of this diagnostic tool will arm oncologists with knowledge of the most effective drug for eliminating the cancer cells and the ability to monitor the onset of drug resistance during the administration of treatment. These new capabilities will avoid the empirical prescription of cancer therapy and enable the start or modification of existing treatment choices as needed. While this project focuses on the chemosensitivity testing of leukemia cells to tyrosine kinase inhibiting agents and the identification of drug resistance as an initial demonstration of its feasibility, the technical approach is applicable to a spectrum of different cancer types and therapeuticagents.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government