January 8, 2002
MEDIA CONTACT: Amy Heaps
Blood Stem Cells Carry Targeted Genes
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: www.hopkinskimmelcancercenter.org
The Blood Journal of the American Society of Hematology: www.bloodjournal.org