Trial to assess personalized vaccine for aggressive brain tumors
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A first-in-human clinical trial will assess the safety of a personalized vaccine to treat diffuse hemispheric glioma, an aggressive brain tumor.
Diffuse hemispheric glioma often is distinguished by a mutation of the H3-3A gene that disrupts RNA processing.
A dendritic cell vaccine has been engineered to target these genetic mutations, thwarting its effects on cancer behavior and treatment response. Dendritic cell vaccines have demonstrated efficacy for treatment of other types of cancer, including glioblastoma.
The trial initially will enroll adults with a confirmed diagnosis of H3 G34-mutant diffuse hemispheric glioma (DHG). It will expand to include patients as young as 5 years.
Researchers will assess the vaccine’s effect on anti-tumor immune response and survival.
“Immunotherapy has brought a sea change in the treatment of hematologic cancers, even in the initial stages of development,” study principal investigator Anthony Wang, MD, director of the pediatric brain tumor program at UCLA Health, told Healio. “It clearly has a critical role to play in solid tumors, as well. However, for many, it will require significant advances in targeting and controlling its effects, both in terms of revving it up and pumping the brakes.”
Healio spoke with Wang about the historical challenges treating diffuse hemispheric glioma, the rationale for why a dendritic cell vaccine may be effective, and how the trial will unfold.
Healio: Can you provide some background on DHG?
Wang: DHG is a type of glioblastoma, one of the most lethal human cancers. Glioblastomas are fast-growing, infiltrate normal brain as they grow, and adapt to develop resistance to therapies quickly. This particular type of glioblastoma most commonly affects adolescents and young adults, but it also is found in children, so it has a profound impact on patients, families and communities.
Healio: What is the standard treatment for this tumor, and what are the typical outcomes?
Wang: We are only beginning to understand this particular type of glioblastoma, as it was only designated as a disease entity in 2021. The standard treatment for DHG is the same as for other forms of glioblastoma. It includes surgical resection followed by temozolomide and radiation therapy.
Healio: Can you describe the vaccine and why you think it could be effective?
Wang: DHG is defined by a particular histone mutation that results in dysregulation of mRNA processing that can have wide-ranging effects on cell function. The effects of this mutation, in combination with the other gene mutations that characterize DHG, drive the initial development of the tumor. However, we have found that the effects of this mutation also create proteins that can be recognized by the immune system as foreign. This is a novel immunotherapy targeting strategy in brain cancer in general, but it is conceptually very well-suited for DHG specifically.
Healio: Can you tell us more about the trial?
Wang: Because DHG affects such a young demographic, we need to establish safety among adults before bringing this trial to children. Participants will receive a standard three-dose course of dendritic cell vaccine, followed by booster doses 6 months and 12 months later. Once we establish safety for adults, we will introduce this strategy into the pediatric population.
Healio: What are the potential implications of this research?
Wang: I am particularly excited by our new targeting strategy, but this is only the beginning of the innovations our group will be bringing to trial in the near future. I believe that immunotherapy will play a critical role in the successful treatment of many more solid tumors in the near future.
Healio: Is there anything else you’d like to mention?
Wang: Cancers affecting children often are fundamentally different than cancers affecting older adults. The differences between the pediatric and classical forms of glioblastoma encapsulate this distinction very well. We would never have reached this point if not for significant advances in our understanding of the basic biology of pediatric gliomas. Our trial is a great example of the importance of research dedicated to pediatric tumors.
Reference:
- UCLA Health launches clinical trial using personalized cancer vaccine to tackle aggressive brain tumors in adolescents and young adults (press release). Available at: https://www.uclahealth.org/news/release/ucla-health-launches-clinical-trial-using-personalized. Published Aug. 5, 2024. Accessed Aug. 22, 2024.
For more information:
Anthony Wang, MD, can be reached at acwang@mednet.ucla.edu.
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