Antibody-based Targeting of Breast Cancer Stem Cells
| Institution: | University of California, Santa Barbara | ||
| Investigator(s): |
Claudia Gottstein , M.D. -
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| Award Cycle: | 2009 (Cycle 15) | Grant #: 15IB-0049 | Award: $150,000 |
| Award Type: | IDEA | ||
| Research Priorities | |||
| Innovative Treatments>Gene therapy and other treatments: new frontiers | |||
Initial Award Abstract (2009)
Breast cancer is a very heterogeneous disease and different patient subgroups vary drastically in clinical outcomes. While the chances to achieve a complete remission are comparatively good in breast cancer, reoccurrence of the disease remains a major problem. A recently developed hypothesis suggests that cancer stem cells, a subpopulation of tumor cells with the ability to self-renew or differentiate into more mature cancer cells, are the major drivers of tumor propagation and metastasis, and potentially tumor recurrence. A cell surface protein marker, called CD44, has been used as a marker for breast cancer stem cells. While CD44 is not an ideal therapeutic target due to its wide expression on many cell types, it can be used to guide identification of other biomarkers co-expressed on CD44 positive breast cancer cells. However, a selection technique that identifies co-expressed markers on specific cell types has not been developed and is the focus of this research. We will utilize a novel approach to detect breast cancer stem cell biomarkers using antibodies (Ab). Our initial work will be to screen large combinatorial phage (virus) libraries prepared from patient lymphocyte samples against archived breast tumor tissue samples. Our goal is to isolate Ab-derived protein sequences on the phage which bind to markers co-expressed with CD44 on breast cancer cells. We anticipate isolating a panel of Ab binding to breast cancer stem cells that we can produce in larger quantity using recombinant expression in bacteria (E. coli). We will test these Ab to: (1) further validate the “stem cell hypothesis” for breast cancer, (2) define stem cell “expression signatures” for stratification breast cancers for better targeted treatment therapies, and (3) use as a basis to make additional cancer stem cell specific monoclonal antibodies (mAb) for targeted therapies Our project is true “high risk-high reward”, and we hope that the Ab generated from our approach will allow to further characterize cancer stem cells and serve as candidates for targeted therapies against breast cancer in patients.
