The ROR1 cell surface biomarker is expressed on B-cell Chronic Lymphocytic Leukemia (B-CLL) cells but not on healthy B-cells or other white blood cells (WBCs) in B-CLL patients. We propose to develop an inexpensive, easy-to-use, rapid, ultrasensitive assay specific for ROR1 for the detection and monitoring of B- CLL from a single drop of blood. Our goal is to attain detection levels better than currently available methods, the most sensitive flow cytometry (MRD-FC) or equal to polymerase chain reaction (ASO-PCR) methods available to detect Minimal Residual Disease (MRD). Early detection of MRD is critical in managing therapy and detecting the emergence of drug resistant malignancies. Current methods are expensive with regard to instruments, reagents, and the need for highly trained technicians. Moreover, FC methods do not adequately differentiate between B-CLL and other clonal B-cell malignancies such as mantle cell lymphoma and splenic marginal zone lymphoma. Current tests require venipuncture to collect 1-3 mLs of blood and the time to results are hours for FC and a week for ASO-PCR. JBI possesses a platform technology to address these shortcomings. JBI's first use of its technology resulted in the ZivaTM Ultrasensitive BrdU Cell Proliferation assay. Using only 50
AIM 2 : To develop and optimize the analytical performance of the ROR1/CLL pilot assay using cell lines.
AIM 3 : To preliminarily evaluate the ROR1/CLL assay performance characteristics using clinically relevant samples.
This grant proposes to develop an ultrasensitive, inexpensive, easy-to-use, rapid diagnostic assay, that is specific for the detection of the ROR1 cell surface biomarker on B-CLL cells, for the detection and monitoring of B-cell Chronic Lymphocytic Leukemia (B-CLL) using a single drop of blood. Developing rapid, inexpensive and easy-to-use diagnostic tools that are better in sensitivity than the most sensitive flow cytometry or PCR methods, using a single drop of blood, presents a very broad public health benefit;for basic cancer research and for patient management worldwide. Furthermore, successful completion of this project is expected to result in a more useful method to differentially diagnose B-CLL from other clonal B cell malignancies such as mantle cell lymphoma and splenic marginal zone lymphoma. The SBIR funds requested in this proposal will accelerate the introduction of an important new technology for the detection of rare cell surface markers for use in both the research and medical communities.