Researchers seeking a way to destroy the cells that develop into brain tumors need look no further than the immune system, according to City of Hope scientists. Their study findings point to a way to eliminate persistent disease.
One of the longstanding frustrations about cancer therapy is that the disease often returns despite chemotherapy, radiation and other treatments. Scientists believe that certain primitive cells — cancer stem cells — can resist these treatments and lie in wait to cause cancer recurrence later.
 The team’s study made the cover of Cancer Research. (Photo by Darrin S. Joy) |
A team led by Christine Brown, Ph.D., assistant research professor, and Michael C. Jensen, M.D., associate chair, both from the Department of Cancer Immunotherapeutics and Tumor Immunology, recently showed disease-fighting T cells may provide a way to destroy cancer stem cells once and for all.
The researchers focused on cytotoxic T cells, or CTLs, which are specialized white blood cells that seek out and destroy bacteria and other invading pathogens.
Reporting in the Dec. 1, 2009, issue of Cancer Research, the team found that CTLs could be “trained” to recognize and destroy brain cancer stem cells resistant to other treatments.
In the study, the researchers took human CTLs that could recognize a length of protein, called a peptide, from a common virus. When these CTLs encounter a cell that contains that viral peptide, they routinely attack and destroy the cell immediately.
The researchers aimed to evaluate the ability of CTLs to kill cells from patients with glioma, the deadliest form of brain cancer. For their tests, they experimented with two kinds of cells: glioma stem cells and glioma cells that were sensitive to drugs.
None of these glioma cells naturally had the viral peptide, but the researchers put the peptide in the cells artificially.
The scientists then compared how the virus-specific CTLs responded to both the regular brain cancer cells with the peptide and the brain cancer stem cells with the peptide.
They saw no difference. The cancer stem cells had no special resistance to CTLs.
“There is nothing intrinsic within the tumor stem cells that makes them resistant to CTL killing,” said Brown. That is important because it opens the door to making CTLs that can obliterate malignant stem cells normally resistant to traditional therapies and prevent the cancer from returning after treatment, she said.
The team next is looking to find unique proteins that naturally arise on the surface of brain cancer stem cells. These might be used to train CTLs to attack the malignant cells, much as the viral peptide was used in the experiment.
Brown cautioned that more study is needed, including work to find and understand other mechanisms that might prevent the CTLs from attacking brain cancer stem cells in the body.
Grants from the National Cancer Institute, the National Institutes of Health, the General Clinical Research Center and Joan and Larry Flax supported the research. Other City of Hope researchers on the study include Renate Starr, Catalina Martinez, Brenda Aguilar, Massimo D’Apuzzo, M.D., Ph.D., Ivan Todorov, Ph.D., Chu-Chih Shih, Ph.D., and Behnam Badie, M.D.