Evidence from the QIMR Berghofer Medical Research Institute suggests that training a person’s T-cells to attack infections of cytomegalovirus (CMV) through an immune system response may also eliminate aggressive forms of brain cancer as collateral damage. The results of this successful Phase I clinical trial study were published in the journal Cancer Research. Though the treatment is still far from a magic-bullet cure for cancer, the collateral damage approach to curing brain cancer does buy patients with quickly declining health more time.
The study specifically examined patients with the kind of brain cancer known as glioblastoma multiforme (GBM). GBM is the most malignant kind of brain cancer known to man. Even with surgery, chemotherapy, and radiotherapy, fewer than ten percent of afflicted patients will survive five years beyond the date of their diagnosis. After only three months, more than half of patients will have succumbed to their cancer or the related neurological conditions that stem from it.
Given that there is a great need to develop treatment options for people with GBM, a study team headed by Professor Rajiv Khanna from the QIMR Berghofer Medical Research Institute sought to explore possibilities in recruiting a patient’s own immune system to treat the cancer. To do this, they sought to elicit the immune system to attack an incidental infection of cytomegalovirus. Thus, the brain tumors would be eliminated as collateral damage from the immune response.
Previous research has found that most brain tumors express proteins that are created by the cytomegalovirus (CMV). CMV infects between 50 and 80 percent of adults above age 40 in the United States. However, it is a “silent” virus, meaning that in most people the infection never causes any symptoms. Though it is widely regarded to be a harmless virus to all but the immunocompromised, there is evidence to indicate that CMV aids in promoting malignancy in brain tumors. This meant that the study team could assume that their patients probably were infected with CMV, and also that the virus would have a particularly strong presence in the brain tumors.
To get the patient’s immune system to attack the CMV infection and by extension the brain tumors, researchers first isolated T-cells from the afflicted person. The scientists then “trained” these T cells to recognize and attack CMV or in other words, to have an adaptive immune response, and subsequently injected them back into the patient. If the treatment was successful, the trained T-cells then would be able to identify the CMV antigens that they encountered in the patient’s body – including the CMV harbored in the malignant brain tumors. Specific classes of T-cells, called cytotoxic t-lymphocytes, would subsequently flag these cancerous, virus-infected cells for destruction by the immune system.
The final results of the study were extremely encouraging. Patients that received this treatment are reported to have lived longer than the usual prognosis of six months. Even more, some patients showed no indication of disease progression. This has made researchers quite eager to continue their studies into the next phase of clinical trials. They hope to recruit patients in the earlier stages of cancer development, with the hope that the treatment will be even more effective if administered earlier.
By Sarah Takushi