Identification of Circulating Cancer Stem Cells in Patients with B Cell Malignancies
Disclosure Date:
10/10/2007
C10205: Methods for Detecting and Monitoring Circulating Cancer Stem CellsValue Proposition:
• Novel method to the quantify cancer stem cells from peripheral blood of patients
• Method to identify cells with clonogenic potential to mediate tumor regrowth that are relatively chemoresistant
• Novel techniques to monitor cancer stem cells in patients undergoing treatment
• Method to monitor cancer stem cell targeted therapies
Technical Details: Background
Cancer stem cells have been prospectively identified in several human cancers. From a functional standpoint, these cells are highly specialized since they have the unique capacity to undergo long-term proliferation. Therefore, cancer stem cells are thought to represent the cellular component within human cancers that are ultimately responsible for growth during both initial tumor formation and disease relapse. Despite their enormous growth potential, cancer stem cells in most diseases have been difficult to study because of they are rare and account for as few as 1 in 10,000 to 100,000 total cancer cells. Their rarity has important implications for the clinical evaluation of therapeutic strategies designed to target cancer stem cells. Specifically, effective strategies that target and inhibit cancer stem cells are not likely to produce immediate clinical responses using standard response criteria since these parameters largely measure tumor bulk. Therefore, novel techniques to monitor cancer stem cells in patients undergoing treatment should be useful in monitoring cancer stem cell targeted therapies as well as predicting long-term clinical outcomes.
Technology
Many agents are active in multiple myeloma, but the majority of patients relapse. This clinical pattern suggests most cancer cells are eliminated, but cells with the clonogenic potential to mediate tumor regrowth are relatively chemoresistant. JHU researchers have identified and characterized cancer stem cells from human B cell malignancies that include non-Hodgkin’s lymphoma, Hodgkin’s disease, and multiple myeloma and have developed novel techniques that allow the quantification of these rare cells within the peripheral blood of patients. Specifically, previous data suggested that CD138(+) multiple myeloma plasma cells could not undergo long-term proliferation but rather arise from clonogenic CD138(neg) B cells. The relative sensitivity of these distinct cell types were compared to clinical anti-myeloma agents. The results show that dexamethasone, lenadilomide, bortezomib, and 4-hydroxycyclophosphamide inhibited CD138(+) multiple myeloma plasma cells but had little effect on CD138(neg) precursors in vitro. Clonogenic multiple myeloma cells and stained cell lines were further characterized using the Hoechst side population and Aldefluor assays. Each assay identified CD138(neg) cells suggesting that they possess high drug efflux capacity and intracellular drug detoxification activity. Multiple myeloma cells expressing the memory B-cell markers CD20 and CD27 could give rise to clonogenic multiple myeloma growth in vitro and engraft immunodeficient nonobese diabetes/severe combined immunodeficient mice during both primary and secondary transplantation. Furthermore, both the side population and Aldefluor assays were capable of identifying circulating clonotypic memory B-cell populations within the peripheral blood of multiple myeloma patients. The results suggest that circulating clonotypic B-cell populations represent multiple myeloma stem cells, and the relative drug resistance of these cells is mediated by processes that protect normal stem cells from toxic injury.
Looking for Partners: Commercial applications include the use of these techniques to quantify cancer stem cells from patients with B cell malignancies that include non-Hodgkin’s lymphoma, Hodgkin’s disease, and multiple myeloma may be utilized to isolate and study cancer stem cells from other hematologic malignancies that include acute and chronic leukemias. These techniques many additionally be utilized to isolate and study cancer stem cells from patients with solid tumors and monitor patients with autoimmune diseases.
Publications/Associated Cases: 1. Matsui, W., Wang, Q., Barber, J. P., Brennan, S., Smith, B. D., Borrello, I., et al. (2008). Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Research, 68(1), 190-197.
2. Jones R J, Lin L, Gocke C, Hensley K, Siedner M, Barber J P, et al. Clonotypic B cells circulate in Hodgkin's lymphoma (HL). Blood 2006; 108: 470a
Patent Information:
| Title |
App Type |
Country |
Serial No. |
Patent No. |
File Date |
Issued Date |
Expire Date |
Patent Status |
| Methods for Detecting and Monitoring Circulating Cancer Stem Cells |
PCT: Patent Cooperation Treaty |
United States |
12/743,180 |
8,748,113 |
1/31/2011 |
6/10/2014 |
11/12/2028 |
Granted |
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Inventors:
Category(s):
Clinical and Disease Specializations, Clinical and Disease Specializations > Oncology, Technology Classifications > Diagnostics > In Vitro Diagnostics, Technology Classifications > Research Tools > Assays, Technology Classifications > Diagnostics, Technology Classifications > Research Tools,
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