How Harnessing Your Immune System Can Combat Brain Tumors
Immunotherapy-based strategies may provide new treatment options for patients with glioblastoma.
Contributor: Manmeet Ahluwalia, MD, FACP
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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 the killing of cancer cells.
The idea of using the immune system fighting cancer dates 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 body’s immune system could not impact the central nervous system. However, recent accumulating evidence suggests this is not true, and there appears to be a dynamic interaction with the immune system and the central nervous system.
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 months to 16 months, and fewer than 10 percent of patients survive more than five years. So 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 including rindopepimut, a vaccine that targets a certain compound found in about 25 percent of glioblastoma.
The vaccine recently was granted a Breakthrough Therapy Designation by the Food and Drug Administration (FDA), based on survival benefit in clinical trials in patients with recurrent glioblastoma. The FDA designation is given when preliminary clinical evidence suggests a therapy provides a substantial improvement over existing therapies. A large study of rindopepimut’s effectiveness for newly diagnosed glioblastoma completed enrollment and results are expected next year.
Another vaccine called ICT-107 also showed benefit in a select group of patients with glioblastoma and further, a larger phase III trial is planned. Other vaccines such as SL-701, DCVax-L, SurVaxM, and HSPPC-96 also are undergoing evaluation.
Recent research published in Nature showed that a tetanus booster vaccine could set off an inflammatory response that increased immune cell migration to the lymph nodes, enhancing the effectiveness of a therapeutic vaccine.
There also 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 release the brakes on the immune system, which allows it to attack cancer cells. Ongoing studies include nivolumab, ipilimumab, pembrolizumab and durvalumab.
Other immunotherapeutic approaches include adoptive T cell therapy in which immune cells 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 resistant to other conventional treatments.
Oncolytic viral therapeutic-based strategies use a modified virus that can cause tumor cells to self-destruct, which prompts an immune response against the cancer. Viruses being investigated in glioblastoma include genetically engineered poliovirus, retrovirus, measles virus and herpes simplex virus, among others.
These immunotherapeutic-based strategies provide new therapeutic avenues, and new hope to extend the lives of patients with glioblastoma.
This post is based on one of a series of articles produced by U.S. News & World Report in association with the medical experts at Cleveland Clinic.