DENVER-Organ transplant rejection caused by CD4 T cells could be stopped in the future using a new hybrid antibody developed at National Jewish Medical and Research Center.
In the March issue of Nature Biotechnology, National Jewish researcher Uwe Staerz, M.D., Ph.D., describes a promising new way to "turn off" the CD4 T cell's attack on a transplanted organ. In 1996, Dr. Staerz described how to control CD8 T cells, which also play a major role in organ transplant rejection. Dr. Staerz estimates clinical trials with the hybrid antibody could take place in approximately two years.
The hybrid antibody developed by Dr. Staerz and Yan Qi, M.D., of National Jewish, selectively "turns off" only the CD4 T cells that attack a transplanted organ. The rest of the body's defenses would be unaffected by the hybrid antibody, allowing the immune system to combat other illnesses. "The T cell sees the transplanted cell, but can't be activated against it," Dr. Staerz explains. "Any other immune response, such as the body defending itself against infections, will go on at the same time without being affected."
Current anti-rejection drugs stop organ rejection and completely suppress the body's immune system, sometimes allowing development of pneumonia, cancer, or other diseases or illnesses.
"Everybody who gets an organ transplant gets sick to a certain extent," Dr. Staerz explains. "This treatment could help prevent that."
When available, this treatment could be necessary only for several weeks following a transplant. Current anti-rejection drugs must be taken for the transplant recipient's entire life to control organ rejection. The hybrid antibody activity may eventually destroy the T cells that normally attack the transplanted organ, preventing future organ rejection, Dr. Staerz says.
Because a biological "match" must be made between the donor organ and recipient, the odds of a successful organ match are 1 in 100,000. Using a hybrid antibody for treatment, the chance of a successful match may increase to 1 in 4. There were more than 19,000 organ transplants in the United States in 1996, according to the United Network for Organ Sharing.
T cells, known as the body's "killer cells," act as immune-system defenders.
Recognized as a foreign object, a transplanted organ is attacked by T cells. In
addition, in autoimmune diseases, such as multiple sclerosis, juvenile diabetes
and rheumatoid arthritis, T cells attack the body's own cells. The hybrid
antibody could be used to help people with these diseases, as well.
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