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Can the human immune system be harnessed to control brain tumor growth?

Dr. Pierre Giglio, Director of the Brain & Spine Tumor Program contributed this article.

The human immune system is a complex system of cells, proteins and barriers that have evolved to fight off diseases. The initial association that comes to mind is the system’s ability to protect against a wide range of infections, including bacterial, viral, fungal and parasitic. However, equally important is the immune system’s ability to identify and eliminate “mutated human cells” that form the building blocks of cancer. Patients with severe immunodeficiency diseases may develop highly aggressive cancers as a result of the immune system’s inability to scavenge such abnormal cells. A common example of this is the development of brain lymphomas in acquired immunodeficiency syndrome (AIDS) patients.

Glioblastoma is the most common and aggressive of the primary brain tumors. The infiltrative nature of this cancer and its rapid growth rate make treatment extremely difficult. As a result, progress in brain tumor research has been slow. There is an urgent need for new and better therapies than the existing ones. Such therapies must be safe as well as effective.

Glioblastoma is a complex and heterogeneous tumor best known by the full traditional term glioblastoma multiforme. The appearance on neuroimaging studies such as brain MRI and the pathologic inspection of the tumor specimen after surgery speaks to an enormous complexity with areas of necrosis, blood vessel formation and rapid cell division with “cell stacking”. The bewildering genetic and molecular foundations of this appearance are just now being unraveled. Glioblastoma produces genes that create multiple different proteins within the neoplastic cell and on its surface.

Looking for an answer in the body’s immune system for such a therapy certainly seems logical. This system has been... “fine tuned” over thousands of years of evolution to recognize foreign and harmful cells or microbes and eliminate them at the lowest possible cost to the human host.
 
How can the human immune system be trained to recognize and eliminate a tumor as complex as glioblastoma?

Two upcoming trials at the MUSC Brain & Spine Tumor Program are asking this very question. The first study titled “A Phase II Clinical Trial Evaluating DCVax® – Brain, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme” proposes to study the potential efficacy of a “vaccine” developed by exposing immune cells obtained from patients with glioblastoma with a lysate from the tumor obtained at surgery for tumor resection. The study will compare the progression free survival of patients treated with the vaccine combined with the current standard of care for glioblastoma with patients receiving standard of care treatment alone. Although we normally associate vaccination with prevention rather than treatment, the vaccine used in this trial is similar to traditional vaccines in principle. Cells from the patient’s immune system are exposed to tumor cells and related proteins and then administered to the patient in a series of immunization injections (up to ten immunizations per patient) to stimulate a response against the residual brain tumor.

The second trial titled: “An International Phase 3 Randomized Double-Blind Placebo Controlled Study of Rindopepimut/GM-CSF Versus Placebo Added to Standard of Care Maintenance Temozolomide in Patients With Newly Diagnosed Surgically Resected EGFRVIII-Positive Glioblastoma” is designed to study the effects of an investigational agent vaccine targeting the Epidermal Growth Factor Receptor vIII, a variant of the epidermal growth factor receptor associated with angiogenesis, tumor invasiveness and inhibition of apoptosis.

Following surgical resection and chemo radiation, eligible patients for the above mentioned Phase III clinical trial will be randomly assigned (1:1) to receive either investigational agent vaccine admixed with GM-CSF as an immune stimulator OR placebo vaccine on top of temozolomide monotherapy (TMT). In both arms, patients are treated in 28 day cycles.

Patients will continue treatment with TMT for a minimum of 6 cycles and up to 12 cycles, in accordance with local standards of care until intolerance or disease progression occurs. The investigational agent or placebo vaccine will be dosed until intolerance or disease progression occurs. The outcomes of the two treatment arms will be compared, including overall survival, progression-free survival, safety and tolerability profiles, and patient reported symptom severity.

The outcome of these two trials is greatly anticipated.

Always talk with your health care provider to find out more information.