Targeting Cytomegalovirus as a Novel for Immunotherapy of Glioblastoma Multiforme

Brain Cancer
Shiao-Pei Weathers, MD
The University of Texas MD Anderson Cancer Center

Glioblastomas (GBM) are tumors of the brain that are highly malignant. They are difficult to treat. Therapy usually includes radiation and chemotherapy. The median survival rate is about 14.6 months with less than 10% of the patients surviving five years or longer.

Cytomegalovirus (CMV) has long been associated with GBM. Ninety five percent (95%) of all gliomas have CMV gene products within the tumor. The goal of any therapy is to infiltrate the tumor and kill the cancer cells.

Dr. Rezvani and her team are taking the patients blood, extracting the CMV specific t-cells and growing them in the lab and administering larger amounts of t-cells to fight the GBM. As a standard of care and to help the t-cells infiltrate the tumor, patients are also administered a strong chemotherapy agent, temozolidide.

This study hopes to increase the chance for tumor death or shrinkage and show an increase in patient survival.

Clinical Description

Glioblastomas (GBM) are tumors of the brain that are usually highly malignant (cancerous) because the cells reproduce quickly. Glioblastoma can be difficult to treat and the treatment plan often combines several approaches, including chemotherapy and radiotherapy. Even with intensive therapy the median survival of patients with glioblastoma is only about 14.6 months and less than 10% of patients are expected to survive for 5 years or longer. There is growing excitement over use of the body’s own immune system (so-called cancer immunotherapy) to target glioblastoma.

In this proposal, Dr.Rezvani’s team seeks to improve the outcome of glioblastoma by using the power of the immune system (T lymphocytes) to target cytomegalovirus (CMV), a virus commonly found in glioblastoma cancer cells, but not normal brain tissue. They can now manufacture T cells against CMV in their laboratory to sufficient numbers and quality for use in cancer patients, placing them in an ideal position to begin clinical trials of this immunotherapy in patients with advanced glioblastoma. They are also testing methods that could enhance the ability of infused CMV-specific T cells to kill glioblastoma cells, by genetically modifying them to become resistant to the immunosuppressive effect of the tumor. If successful, these studies could lead to the use of CMV-specific T cells in all patients with glioblastoma.