UCLA Health Initiates Clinical Trial for Personalized Cancer Vaccine Targeting Aggressive Brain Tumors in Youth
Researchers at UCLA Health's Jonsson Comprehensive Cancer Center have launched a pioneering clinical trial to evaluate the safety and efficacy of a personalized cancer vaccine for adolescents and young adults with diffuse hemispheric glioma. Funded by the Department of Defense, this first-in-human trial focuses on targeting the H3 G34-mutant diffuse hemispheric glioma, an aggressive form of brain tumor characterized by a specific H3-3A gene mutation.
Targeting the H3-3A Gene Mutation
This type of glioma is marked by a mutation in the H3-3A gene, which plays a crucial role in histone regulation and RNA processing. These mutations lead to significant disruptions in RNA processing, influencing cancer behavior and response to treatment. The UCLA-developed vaccine is designed to target these genetic mutations, potentially offering a new therapeutic avenue for this challenging cancer.
Dr. Anthony Wang, the director of the Pediatric Brain Tumor Program at UCLA Health and principal investigator of the trial, emphasizes the unique approach of this vaccine. "These cancers exhibit numerous escape mechanisms that allow them to evade current treatments," Wang noted. "Our pre-clinical studies suggest that a targeted cancer vaccine could adapt alongside the tumor, enhancing the elimination of cancer cells."
See also: The Promise of Next-Generation Proteomics in Revolutionizing Cancer Research and Treatment
Mechanism and Manufacturing of the Vaccine
The vaccine operates by harnessing the patient's dendritic cells, potent activators of the immune system, to target the altered RNA products characteristic of this cancer. After activation, these dendritic cells are reintroduced into the patient to stimulate a robust immune response against the tumor cells.
The UCLA Human Gene and Cell Therapy Facility, among the first university-owned facilities in the U.S., will manufacture the dendritic cell vaccine. Dr. Dawn Ward and Dr. Sujna Raval-Fernandes lead the facility, ensuring the production meets FDA standards for quality and purity.
Expanding the Scope of Treatment
The trial initially includes patients over 18 years old and will later expand to younger patients aged five and above with a confirmed diagnosis of H3 G34-mutant diffuse hemispheric glioma. The trial aims not only to improve survival rates but also to provide new insights into the immune response to primary brain cancers and the potential for lasting anti-tumor immunity.
Collaborative Efforts and Research Tools
The clinical trial is the culmination of extensive research by Dr. Wang, in collaboration with Dr. Linda Liau, chair of neurosurgery at UCLA Health, and Dr. Robert Prins, professor of neurosurgery and molecular and medical pharmacology at the David Geffen School of Medicine. Their work focuses on identifying tumor antigens and understanding the immune system's targeting mechanisms.
A key tool in this research is IRIS (Isoform peptides from RNA splicing for Immunotherapy target Screening), developed with professor Yi Xing from the Children's Hospital of Philadelphia. IRIS predicts products of altered RNA regulation that can trigger an immune response, enabling the identification of effective neoantigen targets for the vaccine.
Future Implications
Dr. Liau highlighted the potential impact of this research:
"This clinical trial represents a novel and potentially transformative approach to treating high-grade gliomas in children and young adults. We are optimistic that this research could lead to more advanced studies and eventually a new standard of care for this challenging subtype of brain cancer."
The trial receives support from the Department of Defense, the National Institutes of Health, and generous donors to the UCLA Pediatric Brain Tumor Program.
Topics: Clinical Trials
