http://unisci.com/stories/20021/0110024.htm
10-Jan-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, show 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 turned
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.
In other possible applications of
the technology, it 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 websites:
The Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins
The Blood Journal of the American
Society of Hematology
Copyright © 1995-2002 UniSci
Contact: Amy Heaps
http://www.hopkinscancercenter.org/
http://www.bloodjournal.org/