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2006
John Sampson, M.D., Ph.D.
Duke University
Inactivation of Regulatory T-cells to Enhance Immunotherapy Against
Cytomegalovirus Antigens in Glioblastoma Multiforme
Conventional therapy for patients with malignant gliomas consists of surgery, radiation, and chemotherapy, but is limited by toxicity to normal brain and tissues. The immune system, however, is designed to differentiate normal from abnormal or even cancerous tissues. A number of methods can be employed to train the immune system and, specifically, the T-cells of patients to fight cancer. These methods include vaccines and strategies called adoptive T-cell therapy.
Dr. Sampson and his colleagues have recently made some important discoveries that enhance these approaches toward fighting tumors. The first is the discovery that proteins from the common cytomegalovirus (CMV) are produced in malignant brain tumor cells, but not in normal surrounding brain tissue. Because these viral proteins are foreign to humans, they can induce very strong immune responses. However, patients with malignant gliomas are often profoundly immunosuppressed, although the cause has remained a mystery for over 30 years.
Dr. Sampson and his team recently demonstrated that patients with malignant gliomas possess increased percentages of a regulatory T-cell, called Tregs, that may be responsible. By removing these regulatory T-cells, they show that their immunosuppressive effects are reversed, and normal immune responses are obtained.
The overall goal is to demonstrate that the removal of the Tregs prior to CMV immunotherapy in GBM patients will generate enhanced antitumor immune responses without inducing autoimmunity and thereby help to optimize this promising therapeutic approach.
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