New strategy to turn off the function of a special group of T cells to suppress immune response to tumors

Aug 26 2005

A special stretch of genetic material may turn off the immune suppression that stymies attempts to fight cancer with a vaccine, said researchers at Baylor College of Medicine (BCM) at Houston.

In a report in today's issue of the journal Science, Dr. Rong-Fu Wang, a professor in the BCM Center for Cell and Gene Therapy and Department of Immunology, and his colleagues describe a new strategy to turn off the function of a special group of T cells to suppress immune response to tumors and even infectious diseases.

"Since 1995, many groups have tried to develop a vaccine for the treatment of cancer," said Wang, also a member of the faculty of the BCM Graduate School of Biomedical Sciences. "The only problem is that after 10 years of clinical trials, the data suggest that you can induce (cancer) antigen-specific immune responses, but such responses are too weak and transient to eradicate tumor cells."

The answer lies in a group of cells called CD4+ regulatory T cells (Treg for short). These cells have the ability to suppress the body's natural immune response. If they are depleted, autoimmune diseases will result because the immune system is unchecked and goes on to attack the body's own tissues.

His group previously reported the existence of tumor-specific Treg cells at tumor sites. "Thus, the tumor cells use these Treg cells to protect themselves," said Wang. "In fact, tumor cells can actively recruit and activate them to turn on their immune suppressive function."

One way to stop this action is to simply wipe out the cells with chemoagents or a specific antibody.

"But you may also deplete the good cells needed for fighting cancer," said Wang.

He and his group identified particular ligands (a special stretch of guanosine-containing DNA material) that can bind specifically to a particular receptor called human Toll-like receptor 8 and then turn off the suppressive function of Treg cells.

Treatment of Treg cells with these ligands converts suppressive Treg cells into non-suppressive T cells.

"In fact, in some cases, this treatment actually enhanced anti-tumor immunity," he said.

He hopes that clinical trials with these special ligands in patients with cancer can get underway quickly.

"It could have a huge impact on cancer therapy or treatment of infectious disease," said Wang. "It could boost response to cancer vaccine as well."