Above: Figure 1: overview of treatment with rindopepimut for EGFR-vIII positive glioblastoma
cells containing the EGFRvIII protein. When bound to tumor cells, these antibodies trigger a regulated process whereby the tumor cells are cleared from the body. As another line of defense, the vaccine also induces immune cells in the body to fight tumors independent of antibody binding. Together, this carefully controlled vaccine-mediated response consistently eliminates all tumor cells containing the EGFRvIII protein. In several phase II clinical studies, vaccination with rindopepimut extended the survival of patients with glioblastoma by an average of nearly one year, when given in addition to conventional therapy. Since the EGFRvIII protein is found exclusively in tumor cells, the vaccineinduced immune response leaves normal cells in the body unharmed. The only side effect reported among the majority of patients who received rindopepimut vaccinations was some mild skin discomfort on the upper thigh where the vaccine was injected. The rindopepimut vaccine has now
advanced to an international phase III clinical trial being conducted at over 100 medical centers across the world.
Dendritic cell vaccines and adoptive T-cell therapy Another strategy, dendritic cell vaccines, has also produced promising results for brain tumor patients. Dendritic cells, also known as professional antigen presenting cells (APCs), play a critical role in the immune system. They capture large molecules from their surroundings, chop the large molecules up into smaller pieces, and then display the small processed fragments on their surfaces. With these fragments on their surface, dendritic cells can direct T-cells, as well as other immune cells, to attack, kill, and eliminate cells containing the originally captured molecule. To exploit this process, dendritic cells taken from a patient’s blood are incubated with tumor molecules isolated from a patient’s tumor. The prepared dendritic cells, with processed tumor molecules
on their surface, are then injected back into the patient where they proceed to orchestrate an assault against the tumor. In other clinical trials T-cells, one of the body’s most deadly weapons against tumor cells, are being modified to increase their activity against brain tumors in what is termed adoptive T-cell therapy. T-cells have the capability to seek out and destroy tumor cells. Under the right conditions, when a T-cell recognizes a tumor cell, the T-cell releases deadly molecules that enter the tumor cell and trigger a cascade of events resulting in death of the tumor cell. Unfortunately, in many patients, T-cells that recognize tumors are short in supply. However, by harvesting T-cells from a patient’s blood or tumor tissue, scientists are able to induce tumor reactive T-cells to replicate, or even introduce new molecules into T-cells that enhance their ability to recognize tumor cells. With an abundance of highly-specific tumorreactive T-cells in hand, clinicians are able to inject these cells back into patients producing highly-successful outcomes, even among patients with late stage disease. n
From the IBTA E News November 2012 3D Neurosurgery: An electrical engineer who underwent four operations for a brain tumour nineteen years ago has invented a 3D endoscope which was used for the first time in Canada last month to remove a brain tumour. More than a dozen hospitals already use the device in the USA where it was approved by the FDA about 18 months ago. Meanwhile, the US National Institutes of Health (NIH) has given a USD $2m grant to researchers at the University of Maryland to continue with their development of a “Minimally Invasive Neurosurgical Intracranial Robot” which may assist in the removal of difficult-to-reach brain tumors. n
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