Immunotherapy is a form of treatment that uses a person’s immune system to fight diseases like cancer. This can be done by either stimulating the patient’s own immune system to work more efficiently to attack cancer cells or giving patients immune system components, such as manmade immune system proteins to enable killing of cancer cells.
The role of the immune system fighting cancer dates back to more than a century ago when William Coley, MD, a surgeon in New York, made the observation that an infection after surgery helped cancer patients. In the last few decades — and particularly in the last 10 years — there has been a resurgence of interest in immunotherapy in general oncology, as well as in brain tumors.
Initial concern about the role of immunotherapy in brain tumors was due to the belief that the central nervous system was an immune privileged site. However, recent accumulating evidence suggests this is not true, and there appears to be a dynamic interaction with the peripheral systemic immune system and the CNS.
Glioblastoma is the most common primary malignant tumor of the brain, and despite the advances in surgery, radiation and chemotherapy, it’s still associated with a dismal outcome. The average survival is 15 to 16 months, and fewer than 10 percent of patients survive more than five years. Hence, there’s an urgent need for promising therapeutic options to improve the survival in this patient population, and immunotherapeutic approaches offer a premise of long-term tumor control for at least a subset of these patients.
The immunotherapeutic approaches being investigated in glioblastoma include vaccine-based approaches such as rindopepimut, ICT-107, SL-701, DCVax-L and HSPPC-96. Rindopepimut (Rintega®) is a therapeutic vaccine that targets EGFRvIII, a mutant peptide expressed in approximately 25 percent of glioblastoma. The vaccine recently was granted a Breakthrough Therapy Designation by the Food and Drug Administration, based on survival benefit in a randomized phase II trial (ReACT) in recurrent glioblastoma patients. A randomized phase III trial of rindopepimut in newly diagnosed glioblastoma has completed enrollment. A randomized phase II trial of the ICT-107 vaccine showed benefit in a select group of patients with glioblastoma, and a phase III trial is planned. Other vaccines undergoing evaluation in randomized phase II or III trials include DCVax-L and HSPPC-96. Recent research published in Nature showed that a strategy that utilized tetanus booster vaccine could set off an inflammatory response to prep the immune system to increase dendritic cell migration to lymph nodes. This enhanced the effectiveness of a vaccine that targeted an antigen from cytomegalovirus.
There is considerable excitement about the use of immune checkpoint inhibitors in glioblastoma. These agents have demonstrated promising activity in melanoma, lung cancer and kidney cancer. They work by targeting molecules that serve as checks and balances on immune responses, and thereby releasing the brakes on the immune system enabling the T cells to attack cancer cells. Ongoing studies include nivolumab (anti-PD1 antibody), ipilimumab (anti-CTLA-4 antibody), pembrolizumab(anti-PD1 antibody) and durvalumab (anti-PD-L1 antibody).
Other immunotherapeutic approaches include adoptive T cell therapy that involve T cells, which are removed from a patient, genetically modified or treated with chemicals to enhance their activity and then given back to patients. This approach has shown to be promising in cancers refractory to other conventional treatments. Oncolytic viral therapeutic-based strategies use a modified virus that can cause tumor cells to self-destruct, thereby facilitating an immune response against the cancer. Viruses being investigated in glioblastoma include genetically engineered poliovirus, DNX-2401, measles virus, Toca 511 (a retroviral replicating vector that expresses the cytosine deaminase gene) and herpes simplex virus.
These immunotherapeutic-based strategies provide not only novel therapeutic avenues, but also new hope to extend the lives of patients with glioblastoma.
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Harnessing the Immune System to Combat Aggressive Brain Tumors originally appeared on usnews.com
