We are applying to establish a monoclonal antibody (mAb) and protein/tissue array facility that will allow us to accelerate the generation and characterization of mAbs generated against embryonic, normal adult tissue and tumor stem cells from a wide variety of tissues and developmental stages. MAbs are one of the most powerful tools we have for the study of stem cell biology. mAbs alone or more often in combination, can be used to isolate cell subsets, to identify cells in tissues in histological section as well as to therapeutically target specific cells. We have a long history of generating mAbs and using them to prospectively isolate and characterize stem and progenitor cells . Cancer stem cells are the cells within a tumor that are responsibly for initiating and maintaining the tumor. the generation of tools that recognize these cells specifically will facilitate the study of those cancers and the development of effective therapies to treat them. Tools that recognize tissue specific stem cells derived from embronic stem cells will facilitate the understanding of normal tissue and organ development and facilitate research that will lead to regenerative medicine therapies. There is a great need for additional tools such as these in stem cell research. By screening these mAb libraries against a wide variety of cells and tissue microarrays we can efficiently and cost effectively identify useful reagents that will help identify and quantify cancer stem cells and tissue derived or ESC derived stem cells in vivo and in vitro. The novel mAbs generated and characterized in this proposal, after filing for intellectual property protection, will be useful tools available to the entire CIRM community and can be further developed for research, diagnostic and therapeutic applications.
The principle objective of this proposal is to develop and screen antibodies, which, alone or more likely in combinations, can identify and isolate cancer stem cells, adult stem cells and tissue-regenerating stem cells derived from hESC lines. Antibodies are highly specific and powerful tools that can be used for research, diagnosis and therapeutic applications. We have also found that antibodies generated against stem cell antigens in one tissue often recognize the antigens present in other tissues as well. By screening the antibodies against dissociated cells as well as tissue microarrays of both normal and cancerous tissue we will be able to optimize the identification of useful clones. We have several libraries in development and propose to generate others. The antibodies and the cancer and other stem cells that they will allow to be identified and isolated from patients with specific diseases, will be invaluable tools that can be used to characterize their biology, to create model(s) for understanding the diseases and their progression, and to develop therapies.
In addition, the antibodies generated in these studies are entities that could be patented or protected by copyright, forming an intellectual property portfolio shared by the state and the state institutions wherein the research was carried out. The funds generated from the licensing of these technologies will help pay back the state, will help support increasing faculty and staff (many of whom bring in other, out of state funds for their research), and could be used to ameliorate the costs of clinical trials. Only California businesses are likely to be able to license these antibodies and cells, to develop them into diagnostic and therapeutic entities; such businesses are the heart of the CIRM strategy to enhance the California economy. The most important impact, however, is that this research will lead to cancer and tissue stem cell therapies. In the case of cancers, targeting the cancer stem cells specifically should be much more effective than nonspecific antiproliferative therapies that the cancer stem cells are often less sensitive to than the bulk of the tumor. In the case of tissue regenerating stem cells, such therapies will address chronic diseases that cause considerable disability and misery, currently have no cure, and therefore lead to huge medical expenses. Because tissue stem cells renew themselves for life, stem cell therapies are one-time therapies with curative intent. We expect that California hospitals and health care entities will be first in line for trials and therapies, and for CIRM to negotiate discounts on such therapies for California taxpayers, thus California will benefit both economically and with advanced novel medical care.