Stretching the Timeline: Innovation in Glioblastoma Vaccination

Authored By: Kate Constan

Art By: Alex Peng

The prospect of vaccinating for cancer treatment sounds fantastical. 

The prospect of surviving a glioblastoma—a malignant brain cancer that has a 5% survival rate 5 years after diagnosis—sounds equally far-fetched. Now, a series of clinical trials on dogs, mice, and a handful of human subjects, has ended. The possibility of a glioblastoma (GBM) vaccine no longer seems unrealistic: the results are promising, and these vaccines have shown lengthened survival timelines. 

Glioblastoma is an aggressive form of brain cancer that has historically proven to be resistant to treatment. Standard care typically involves surgery, followed by radiation and chemotherapy. However, these therapies rarely achieve lasting outcomes. Even after intense treatment, glioblastomas frequently recur and survival rates remain alarmingly low. Similar to other poor-prognosis cancers, this form often evades the immune system’s usual defense mechanisms, resulting in an especially unrelenting tumor [1]. 

Like many others, my family experienced firsthand how these standard treatments were unsuccessful. My grandfather was diagnosed with GBM in 2021, and lived just a few months before passing away. Between several surgeries and radiation treatments, the doctors worked hard to salvage those last months and lengthen the amount of time he could spend with his family. As of 2021, GBM posed an inescapable challenge. 

As it is the source of personal tragedy, I have closely followed advancements in glioblastoma treatment. This past year, I have found hope in the prospect of using novel vaccines to treat GBM. Vaccines typically work by priming the immune system to recognize and attack harmful pathogens. The challenge in creating a glioblastoma vaccine lies in the fact that the immune system does not always identify glioblastoma cells as dangerous—cancer cells belong to our own bodies, not pathogenic invaders. To overcome this, researchers have developed cancer vaccines that enhance the immune response to these tumors, helping the body recognize and destroy the cancerous cells [2]. 

In 2024 pre-clinical trials, researchers at the NCI Center for Cancer Research found high efficacy in a cancer vaccine that can activate immune cells to recognize and attack glioblastomas (CCR). The rWTC-MBTA vaccine works by activating the immune system to recognize and attack GBM tumor cells. It contains irradiated tumor cells, which are modified so they can't grow but still trigger an immune response. These cells are combined with MBTA, a mix of ingredients including a yeast-derived sugar, which then attracts immune cells. Sugar draws immune cells to the tumor, while other MBTA components enhance the immune response. This process stimulates immediate and long-term immunity to the tumor, shrinking tumor size in models [2].

While these results are fascinating and promising, the senior author of the study, Dr. Zhengping Zhuang, noted that the vaccine is “not a cure-all” [2]. The intention behind many of these innovations is not survival, but rather the extension of life and improvement of quality-of-life in GBM patients.

Another such innovation involves dendritic cell vaccines. Researchers across 94 sites worldwide (published in 2022 in JAMA) and, more recently, several universities in Italy (published in 2024 in Frontiers) investigated these vaccines in clinical trials. They are created by extracting a patient’s dendritic cells and combining them with antigens derived from the patient’s own tumor cells [3]. The cells are then reinjected into the body, where they stimulate the immune system to attack the cancer [4]. This approach has shown early success, with some patients experiencing prolonged remission following vaccination. The vaccine, referred to as “DCVax” has been proven safe and effective, and the researchers recommend use as part of combination treatment [4]. Once again, these vaccines are not the be-all end-all of GBM treatment.

For patients with newly diagnosed glioblastoma, the median overall survival was significantly extended to 19.3 months from 16.5 months—a striking increase of 2.8 months [3]. Patients with recurrent glioblastoma also showed marked improvements, with a median survival of 13.2 months compared to 7.8. In some patients, the survival benefits are even more meaningful, lasting up to 60 months [3].

Another new approach (led by researchers at the University of Florida) to glioblastoma treatment involves the use of multi-lamellar RNA lipid particle aggregates (LPAs). These LPAs enhance the packaging and immunogenicity of tumor mRNA antigens, triggering an immune response in stromal cells [5]. This approach has led to rapid immune activation in both animal models and human trials. In a groundbreaking first-in-human trial, LPAs improved survival in glioblastoma patients and elicited glioma-specific immune responses, marking a potential breakthrough in cancer immunotherapy [5]. This breakthrough made major headlines in 2024, and could lay the groundwork for glioblastoma vaccines to be made widely available.

While glioblastoma vaccines are still in the experimental stage, their success offers hope for the future of cancer treatment. These vaccines represent a fundamental shift toward more targeted, immune-based therapies for cancer. For those of us who have lost loved ones to glioblastoma, the promise of these innovations is both a source of solace and a reminder of what might have been. I hope for a future where patients like my grandfather are able to access novel treatments and live longer, surrounded by their families.

1. Medikonda, R., Dunn, G., Rahman, M., Fecci, P., & Lim, M. (2020). A review of glioblastoma immunotherapy. Journal of Neuro-Oncology, 151(1), 41–53. https://doi.org/10.1007/s11060-020-03448-1 

2. A new vaccine to target treatment-resistant glioblastoma. Center for Cancer Research. (2024). https://ccr.cancer.gov/neuro-oncology-branch/a-new-vaccine-to-target-treatment-resistant-glioblastoma 

3. Liau, L. M., Ashkan, K., Brem, S., Campian, J. L., Trusheim, J. E., Iwamoto, F. M., Tran, D. D., Ansstas, G., Cobbs, C. S., Heth, J. A., Salacz, M. E., D’Andre, S., Aiken, R. D., Moshel, Y. A., Nam, J. Y., Pillainayagam, C. P., Wagner, S. A., Walter, K. A., Chaudhary, R., … Bosch, M. L. (2023). Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma. JAMA Oncology, 9(1), 112. https://doi.org/10.1001/jamaoncol.2022.5370 

4. Ridolfi, L., Gurrieri, L., Riva, N., Bulgarelli, J., De Rosa, F., Guidoboni, M., Fausti, V., Ranallo, N., Calpona, S., Tazzari, M., Petrini, M., Granato, A. M., Pancisi, E., Foca, F., Dall’Agata, M., Bondi, I., Amadori, E., Cortesi, P., Zani, C., … Tosatto, L. (2024a). First Step results from a phase II study of a dendritic cell vaccine in glioblastoma patients

5. Mendez-Gomez, H. R., DeVries, A., Castillo, P., von Roemeling, C., Qdaisat, S., Stover, B. D., Xie, C., Weidert, F., Zhao, C., Moor, R., Liu, R., Soni, D., Ogando-Rivas, E., Chardon-Robles, J., McGuiness, J., Zhang, D., Chung, M. C., Marconi, C., Michel, S., … Sayour, E. J. (2024). RNA aggregates harness the danger response for potent cancer immunotherapy. Cell, 187(10). https://doi.org/10.1016/j.cell.2024.04.003