UCLA researchers in the Departments of Neurosurgery and Microbiology, Immunology, and Molecular Genetics have developed an immunotherapy treatment methodology for H3G34R/V high-grade glioma, providing an ability to be adapted toward a wide range of similar tumors.
BACKGROUND:
Over 3000 gliomas and other forms of brain cancer are diagnosed in children and adolescents every year. These unique brain tumors can cause a wide range of debilitating symptoms such as double vision, headaches, and nausea: often worsening with disease progression. The most dangerous variants, known as high-grade gliomas, can be particularly devesting due to rapid growth if not diagnosed early, then treated immediately. Unfortunately, treatment options for these gliomas have been limited to small molecule chemotherapeutics or radiation therapy: both offering major unintended side effects due to cytotoxicity observed in cancerous and healthy cells alike. Further exacerbating this issue, is the problem with adequate concentrations of small molecule therapeutics crossing the blood brain barrier (BBB) to be effective in killing cancerous cells. As a consequence, many glioma cases rapidly progress if the tumors have not been detected early enough before rapid expansion. More targeted forms of therapy like surgical interventions are often reserved as a last resort, due to proximity of the brain, and unfortunately have a wide margin of effectivity. Therefore, there is a need for the development of treatments that can specifically target gliomas and penetrate the body’s natural defenses to traditional forms of treatment.
INNOVATION:
UCLA researchers in the Departments of Neurosurgery and Microbiology, Immunology, and Molecular Genetics have developed an immunotherapy treatment methodology for H3G34R/V gliomas. By engineering T cells to target a unique set of markers found only on these tumors, researchers have been able to develop a highly specific therapy to combat H3G34R/V high-grade gliomas. The therapy has been rigorously tested in cellular and murine models, demonstrating high potential to eliminate tumor cells. Furthermore, the murine models treated with these therapies displayed significantly longer survival rates in comparison to both treated control models, as well as those receiving treatment controls. The immunotherapy agent is highly specific for H3G34R/V glioma cells, obviating the toxicities common with current standard chemotherapies and radiation therapy. As a consequence, the proposed therapy may prove useful in tumors that have not been diagnosed early and have rapidly expanded. It should be noted that the administration of adjuvant treatments of various modalities can be administered concurrently or in sequence, expanding the potential to stop aggressive tumor growth. While the proposed immunotherapeutic is designed to treat H3G34R/V high-grade gliomas, the methodology could be expanded to treat cancers carrying similar cellular targets.
POTENTIAL APPLICATIONS:
• Treatment of Brain Tumors
• Animals Research Studies
ADVANTAGES:
• Specifically targets H3G34R/V mutant tumors
• Targeted vaccines can be created without the need for tumor tissue, allowing for more options in timing of treatment delivery
• Different side effect profile compared to current standard-of-care treatments
DEVELOPMENT-TO-DATE:
The treatment has been tested in cellular and murine models. In murine models, treated mice showed, on average, significantly longer survival rate compared with controls. Additionally, a significant proportion of treated mice witnessed complete and lasting tumor elimination, which was not seen in controls.