A Way to Target a Molecule That Lets the Tumor Grow
GAINESVILLE, Fla. — Glioblastoma is an aggressive, stubborn brain tumor with low odds of survival for patients. Now, University of Florida Health researchers have found a way to target a molecule that lets the tumor grow, migrate and evade the body’s immune system.
The molecule, known as CD70, is found on the surface of glioblastoma tumors. Targeting its abnormal activity with state-of-the-art immunotherapy techniques led to a profound antitumor response during testing on human cancer cells and animal models, researchers said. The findings were published recently in two journals, Neuro-oncology and the International Journal of Oncology.
“We think this finding shows the vast potential of immunotherapy and holds promise for glioblastoma cancer treatment,” said Jianping Huang, M.D., Ph.D., an associate professor in the Lillian S. Wells department of neurosurgery at the UF College of Medicine.
In addition to being pernicious — the five-year survival rate is less than 10 percent — glioblastoma was thrust into the headlines when U.S. Sen. John McCain, R-Ariz., was diagnosed and had a tumor removed.
The UF researchers discovered that a T cell, a type of white blood cell, can be extracted from a patient and genetically reprogrammed to recognize and attack glioblastoma tumors that feature CD70. Receptors on the T-cell’s surface bind to a specific protein on glioblastoma cells, a process called chimeric antigen receptor T-cell, or CAR-T cell, therapy. The CAR-T cells function like a genetic “off” switch, silencing the CD70 gene and stopping the tumor’s ability to evade the body’s immune system.
After demonstrating that the CAR-T cells were able to kill their specific tumor targets in mouse and human cells, researchers found similar success using mouse models. Among a group of mouse models that were treated with CAR-T cells, 38 percent were cured of their tumors and survival was “significantly prolonged” for others.
“Our preclinical studies have shown that CD70-specific CAR-T cells can kill tumor cells derived from patients and that tumor-bearing animals were cured or survived longer when treated,” Huang said.
No negative side effects were found, researchers said, suggesting the therapy is both potent and safe.
“I believe the work advanced by Dr. Huang and her colleagues holds significant potential for the advancement of desperately needed new therapeutic options for glioblastoma and other cancers. The clinical development of this novel CAR-T cell immunotherapy for CD70-positive brain tumors is a high priority for the UF Brain Tumor Immunotherapy Program,” said Duane Mitchell, M.D., Ph.D., a neurosurgery professor and the immunotherapy program’s director, who also co-authored the two papers.
Ultimately, Huang said, the goal is to translate the therapy to glioblastoma patients. Next, Huang and her collaborators want to study the effects of combining CAR-T therapy with other anti-tumor treatments. Preliminary data from mouse models show that localized radiation can improve the homing and anti-tumor activity of CAR-T cells, she said.
While the findings are encouraging, Huang noted that CAR-T therapy won’t help everyone. About 35 percent of newly diagnosed glioblastoma patients — and a higher percentage of patients with recurring tumors — are carrying the CD70 molecule. Among that group, not everyone has the CD70-positive cells that are needed for the treatment to work.
Huang, a member of the Evelyn F. And William L. McKnight Brain Institute of the University of Florida, collaborated with researchers from the National Cancer Institute and Harbin Medical University in Harbin, China, on the two projects. Funding was provided by the American Cancer Society, the Wells Endowment, and the Ministry of Science and Technology of the People’s Republic of China.