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Blood Stem Cells Carry Targeted Genes1-10-2002 Researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have genetically altered human blood stem cells to selectively activate genes in developing immune cells. Results of the research in mice, published in the January 15 issue of Blood, shows it's possible to transfer genes into stem cells and activate the immune system to fight cancer and enhance transplantation. "Blood stem cells represent an important target for the treatment of a variety of blood and immune disorders, so our ability to engineer them to selectively stimulate immune responses opens up new possibilities for gene therapy," says Linzhao Cheng, Ph.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center and director of the study. Using a gene known to produce a fluorescent protein, scientists transferred it into human adult and cord blood stem cells and injected the cells into immune-compromised mice. The gene transfer into the stem cells was accomplished via a lentivirus, genetically engineered to be safe, with coded instructions for the gene to turn on in a specific type of cell. Since blood stem cells differentiate and develop into all blood and immune system cells, all descendants of the stem cells had the fluorescent protein gene. However, the gene turns on only when the stem cell developed into one type of immune cell, called an antigen-presenting cell (APC). APCs play a central role in controlling immune system responses. |
"The ability to deliver a gene in a stem cell and then have it expressed in one specific type of cell should provide a new way to achieve targeted gene therapy," says Cheng. Six mice were transplanted with the fluorescent gene made specific for APCs. After 10 weeks, all produced the fluorescent protein in an average of 56 percent of the transplanted cells, and exclusively in APCs. Five control mice were transplanted with the fluorescent gene made universal for all cells and produced fluorescence in all types of the transplanted cells. Four additional control mice without the fluorescent gene showed no fluorescent protein in any transplanted cells. The researchers will conduct further studies to explore the possibility of delivering genes that boost the immune system to develop stronger therapeutic cancer vaccines. Other possible applications of the technology may be used to suppress the immune system to reduce adult cell transplant rejection. The researchers also will study using this technique to overcome immune system-mediated rejection of embryonic stem cell transplants. No clinical trials are planned at this time. The study is a collaboration between the laboratories of Cheng and Drew Pardoll, M.D., Ph.D., Division of Immunology and Hematopoiesis at the Johns Hopkins Kimmel Cancer Center. Other researchers include Yan Cui, Ph.D., Jonathan Golob, B.S., Erin Kelleher, B.S., and Zhaohui Ye, M.S. from the Johns Hopkins Kimmel Cancer Center. Related Web Sites: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: http://www.hopkinscancercenter.org The Blood Journal of the American Society of Hematology: http://www.bloodjournal.org This article has been adapted from a news release issued by Johns Hopkins Medical Institutions, www.hopkinsmedicine.org. These
statements have not been evaluated by the Food and Drug Administration.
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