UCLA Health is leading a groundbreaking clinical trial to combat one of the most aggressive forms of brain cancer with a personalized cancer vaccine. This pioneering study represents UCLA Health’s inaugural human trial for a vaccine specifically targeting diffuse hemispheric glioma, a malignant brain tumor predominantly affecting adolescents and young adults. The trial, funded by the Department of Defense, the National Institutes of Health (NIH), and generous donors, marks a significant advancement in addressing this issue.

Developed at the UCLA Health Jonsson Comprehensive Cancer Center, the vaccine targets the H3 G34-mutant diffuse hemispheric glioma, distinguished by a mutation in the H3-3A gene which disrupts histone proteins and leads to severe RNA processing disruptions. These mutations significantly influence cancer development and its response to treatment. Initial preclinical trials have shown promising results, and the ongoing clinical trials aim to build on this success, potentially leading to one of the first personalized cancer vaccines.

Diffuse hemispheric glioma is a notoriously aggressive form of cancer that often evades conventional therapies such as chemotherapy. The encouraging early preclinical data is providing hope for researchers and specialists at the Pediatric Brain Tumor Program at UCLA Health. The goal is to translate these preliminary successes into a treatment that can significantly improve patient outcomes.

Manufacturing the vaccine

The vaccine works by enhancing the function of dendritic cells, specialized cells capable of activating immune responses. By boosting these cells, the vaccine aims to help the immune system recognize and target specific changes in the cancer cells’ RNA. These changes, which distinguish the cancer from other forms, enable the immune system to better identify and attack the tumor cells. 

The clinical trial will start with patients age 18 and older and will eventually include younger patients, starting as young as age 5. The primary objective is to improve survival rates among individuals with hemispheric glioma, and potentially extend the lives of those with the devastating cancer. UCLA Health aims not only to target and eliminate this aggressive cancer, but also to develop a long-lasting anti-tumor response that could set a new standard in cancer treatment.

Laying the groundwork for the clinical trial

The development of this vaccine has been spearheaded by Dr. Anthony Wang, who has dedicated years to advancing this innovative treatment. Dr. Wang’s efforts are supported by other leading experts at UCLA Health, including Dr. Linda Liau and Dr. Robert Prins, both renowned for their pioneering work in immunotherapy. Their contributions have been crucial in developing and advancing new treatment strategies.

The vaccine will be manufactured at the UCLA Human Gene and Cell Therapy Facility, a state-of-the-art institution led by Dr. Dawn Ward and Dr. Sunja Raval Fernandes. This facility, one of the first university-owned of its kind in the U.S., is integral to the project’s success. The team is focused on ensuring the vaccine meets stringent FDA standards, including rigorous quality control and adherence to safety protocols. Beyond the glioma vaccine, the center’s mission extends to understanding and preventing a broad range of illnesses and cancers.

Effective cancer immunotherapies require a deep understanding of tumor antigens targeted by the immune system. The histone H3 G34R mutation, central to this research, impacts mRNA regulation, leading to distinctive mRNA splicing changes. These alterations produce neoantigens, novel antigens recognized by T lymphocytes, which are crucial for developing the dendritic cell vaccine.

The IRIS tool (Isoform Peptide from RNA Splicing for Immunotherapy target Screening), developed in collaboration with the Children’s Hospital of Philadelphia, is essential for identifying these neoantigen targets. This computational tool predicts which products of disrupted RNA regulation are likely to elicit an immune response, guiding the vaccine’s development. By pinpointing these targets, the team aims to optimize the vaccine’s effectiveness and improve patient outcomes.

The UCLA Human Gene and Cell Therapy Facility, as well as researchers and clinicians, are optimistic that this new approach will transform the treatment of gliomas and set new standards in cancer care. They believe the targeted cancer vaccines being developed will adapt to these tumors and effectively eliminate cancer cells, offering hope for more effective treatments, especially for younger patients suffering from aggressive brain cancers.

UCLA Health’s dedication to pioneering advanced cancer care reflects its commitment to addressing complex medical challenges and improving patient outcomes. The success of this clinical trial could mark a significant advancement in treating gliomas, potentially offering new hope to those affected by these cancers.

For more information, please visit https://www.uclahealth.org/international-services/ or call +1 310-794-8759