Improving The Potential Of Cancer Vaccines

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 Departmentof Immunology, and his colleagues describe a new strategy to turn offthe function of a special group of T cells to suppress immune responseto tumors and even infectious diseases.

"Since 1995, many groups have tried to develop a vaccine for thetreatment of cancer," said Wang, also a member of the faculty of theBCM Graduate School of Biomedical Sciences. "The only problem is thatafter 10 years of clinical trials, the data suggest that you can induce(cancer) antigen-specific immune responses, but such responses are tooweak 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'snatural immune response. If they are depleted, autoimmune diseases willresult because the immune system is unchecked and goes on to attack thebody's own tissues.

His group previously reported the existence of tumor-specific Tregcells at tumor sites. "Thus, the tumor cells use these Treg cells toprotect themselves," said Wang. "In fact, tumor cells can activelyrecruit and activate them to turn on their immune suppressivefunction."

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.

Heand his group identified particular ligands (a special stretch ofguanosine-containing DNA material) that can bind specifically to aparticular receptor called human Toll-like receptor 8 and then turn offthe 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 ofinfectious disease," said Wang. "It could boost response to cancervaccine as well."

Others who participated in this research include: Drs. Guangyong Peng,Yukiko Kiniwa, Kui shin Voo, Tihui Fu, and Yanchun Li; and Zhong Guo,Weiyi Peng, Daniel Y. Wang, and Helen Y. Wang, all of BCM. Thisresearch was supported by the National Institutes of Health and theCancer Research Institute.