Glioblastoma Awareness Day: What You Need to Know About Immunotherapy’s Battle Against the Deadliest Brain Cancer

Cancer poses numerous treatment challenges, which depend on factors such as the stage of the disease, its extent of spread, and its location within the body. Brain cancers are generally difficult for doctors to treat – partly because their causes are not greatly understood, and unfortunately the mortality rate has remained the same over the past three decades. 

The most common, aggressive, and deadly form of brain cancer is glioblastoma (GBM). 

Why is GBM such a deadly type of cancer? 

Statistically speaking, the prognosis for most GBM patients is dire. Only one in four patients survive beyond two years after diagnosis, and less than 10% outlive the five-year survival threshold. Peter Fecci, MD, PhD, CRI Arash Ferdowsi Lloyd J. Old STAR, and director of both the Brain Tumor Immunotherapy Program and the Center for Brain and Spine Metastasis at Duke University, explained why a GBM diagnosis can be sobering for patients. 

“GBM strikes at the very thing that makes us, us. The types of deficits and changes it elicits in folks are incredibly specific to where in the brain the tumor happens to develop,” Dr. Fecci explained.  

“Even a small tumor can become incredibly unfair with regard to the function it may affect or remove. Anything from personality, to strength, to memory, to language”, he continued. 

GBM forms in astrocytes, which are cells involved in transporting nutrients and repairing other cells. Although it does not often metastasize to other body parts, GBM does spread from its origin site to nearby brain tissue. The American Association of Neurological Surgeons states that GBM presents oncologists with a non-exhaustive list of many diagnostic and treatment challenges: 

1. Localization of tumors within the brain 

2. The brain’s limited ability for self-repair 

3. It disrupts blood supply, impairing effective drug delivery to the tumor 

4. Seizures caused by the GBM tumor 

5. Malignant cells migrating to neighboring brain tissue 

Symptoms and Screening Options 

Certain factors can increase an individual’s GBM risk, such as hereditary cancer syndromes, age, previous therapeutic radiation, and a weakened immune system response. The Mayo Clinic says GBM symptoms can vary depending on its location within the brain, but include: 

1. Vision impairment, such sight that has doubled or is blurry

2. Lengthy headaches 

3. Challenges with brain function, such as a decreased ability to think and learn 

4. Irritability and personality changes 

5. Difficulty maintaining balance and coordination 

The most common way to diagnose GBM is to discuss symptoms with a doctor, have a physical examination, and undergo imaging tests. According to Penn Medicine, computed tomography (CT) scans are one option, but magnetic resonance imaging (MRI) scans are considered the ‘gold standard’ for GBM. Furthermore, advanced neuroimaging can illuminate blood fiber tracts, blood volume, and the tumor’s metabolic function. These tests help monitor tumor recurrence and determine therapeutic response. 

Sean’s GBM Story: From Seizure to Survival

Although GBM presents challenges for oncologists and immunologists, immunotherapy can help patients with this aggressive cancer. During this past Cancer Immunotherapy Month™ in June, CRI featured an “I’M the Answer to Cancer™,” story about Sean Kukolek’s successful GBM immunotherapy treatment. The 20-year-old recalled going to the golf course to get some practice four years ago. The next thing he knew, he was in an ambulance – he had suffered a seizure. He recalled feeling emotionally volatile when he learned about his diagnosis. 

“When I found out the tumor was cancerous, I remember being really angry,” Sean told CRI. “You should allow yourself to feel your emotions. I didn’t just bottle it up.”  

Luckily, Sean was accepted into an immunotherapy clinical trial in Pittsburgh and was treated with Pembrolizumab, commonly known as Keytruda®. The drug is one of six immunotherapies now approved by the U.S. Food and Drug Administration (FDA) for brain cancer patients. It is also important to note Keytruda® just received its 40^th FDA approval. 

“Immunotherapy pokes a hole in the cancer force field so your body can kill it,” Sean explained. “During my trial, they were excited about my story. When you remove a tumor, it leaves a hole. Whatever was holding the hole open, collapsed on itself. It’s good to have some positivity in the cancer world, and some hope.” 

Thanks to Sean’s medical team, his clinical trial, and his support system, he is now cancer-free. In 2023, he graduated from college and now works for Major League Baseball’s Cleveland Guardians. His story is a testament to the power of immunotherapy, even for some of the most aggressive forms of cancer. A clinical trial was instrumental for Sean’s treatment, and there are several other ongoing trials for GBM immunotherapy that could help others. 

CRI Scientists Take the Fight to GBM

CRI is currently funding several scientists who are focusing on brain cancer, including GBM. One of them, Gavin Dunn, MD, PhD, CRI Lloyd J. Old STAR, director of the Center for Brain Tumor Immunology and Immunotherapy at Mass General Brigham, and associate professor at Harvard Medical School, said unlocking how the immune system can effectively recognize glioblastoma cells effectively is critical to producing better treatment options. 

“Current treatments tend to constrain tumor growth for a relatively short period of time,” Dr. Dunn explained. “Every patient with glioblastoma I have ever had the privilege of treating is full of resolve, hope, fortitude, and courage: we owe it to our patients to study their brain cancers and improve their lives.” 

Over the years, CRI scientists have made significant immunotherapy developments to help better GBM patient outcomes. Former CRI Investigator Alex Yee-Chen Huang, MD, PhD, then at Case Western Reserve University, created a new approach to track immune and tumor cell interactions in real time with GBM patients.

Additionally, former CRI Student Training and Research in Tumor Immunology (STaRT) grant recipient Bryan Choi, MD, PhD, then at Duke University, created a bi-specific T cell-engaging antibody (BiTE) to combat the EGFRvIII tumor-specific antigen, which is prevalent in the majority of GBM patients. In March of 2024, Dr. Choi published the results of first human clinical trial based on his research in The New England Journal of Medicine.

“In our recent manuscript we reported our first-in-human experience with a novel therapy platform that combines CAR T cell technology with bispecific antibodies for patients with recurrent glioblastoma.” Dr. Choi stated. “We noted rapid radiographic regression in several patients following intraventricular treatment with CARv3-TEAM-E T cells. Additional patients are currently being treated alongside strategies seeking to enhance durability of this therapeutic response.” 

CRI scientists are dedicated to researching immunotherapy treatments that could greatly benefit GBM patients and dampen the impact of this cancer. With their research, and your support, we can create a world immune to cancer.