LOS ANGELES, May 03 (Reuters) - By blocking an antibody needed to activate
certain white blood cells known as T-cells, researchers at a Seattle cancer
center announced on Tuesday they were able to reduce or prevent the rejection of
transplanted bone marrow in mice.
The discovery could lead to safer and more effective bone marrow and organ
transplants, said Dr. Claudio Anasetti, the study's lead researcher.
Despite advances, graft-versus-host disease is still a major complication
for patients recovering from bone marrow transplantation, a procedure used to
treat patients diagnosed with leukemia, lymphoma and a number of other blood and
genetic disorders.
Graft-versus-host disease occurs when the donor marrow recognizes the
patient's tissue as foreign. Transplanted white blood cells begin mounting an
attack, which results in a number of symptoms ranging from mild to severe, and
in some cases proves fatal. Researchers at the Fred Hutchinson Cancer Research
Center found that treatment with an anti-CD28 antibody could be used to limit
that reaction. CD28 is a T-cell surface structure, the function of which is
pivotal to determine whether or not a foreign protein triggers an immune
reaction.
T-cells recognize and destroy abnormal or infected cells, help other cells
destroy infective organisms and suppress the activity of other lymphocytes so
they do not destroy normal tissue.
"To become activated, human T-cells need to see a receptor. The CD28
receptor is neutralized by the antibody," Anasetti explained. CD28 is a
monoclonal antibody made in a laboratory, but equipped with the capabilities of
natural antibodies.
The researchers said CD28 antibodies may be safer and more effective in
preventing transplant reactions than other immunity-suppressing drugs. The
effect of anti-CD28 is restricted to T cells engaged with the specific
transplant antigen, and the body's immune response to other pathogens --
disease-causing microbes -- is not affected.
Results from the study were published in the May 1 issue of the Journal of
Immunology.
"We expect that such an agent will be useful not only in transplantation of
hematopoietic (blood-forming) stem cells, a primary interest at Hutchinson
Center, but also in the prevention of pancreatic islet, kidney, and other solid
allograft rejection as well as the treatment of autoimmune diseases such as
rheumatoid arthritis and diabetes," Anasetti said.
"However, so far our research has focused on mouse models, the next step is
human trials and now we can quickly move forward to these trials," he said.
