UCLA researchers from the Department of Neurosurgery have characterized immune responses in malignant glioma patients receiving immunotherapy to develop a robust biomarker that will allow prediction of clinical outcomes following treatment.
BACKGROUND: Malignant gliomas are the most common primary brain tumors in adults. No cures exist and most gliomas have high mortality rates. Standard of care therapies are toxic and have not been able to substantially improve long-term health outcomes for patients. Current immunotherapies exhibit varied response rates. Thus, next steps in treating this disease include discovering how to enhance the anti-cancer immune effects of current immunotherapies for malignant gliomas. Additionally, being able to predict whether patients will be responsive to these treatments using biomarkers that can be gathered using minimally invasive techniques (such as peripheral blood draw) is integral to optimizing patient care and improving outcomes for this devastating disease.
INNOVATION: UCLA researchers conducted an in-depth characterization of immune cell profiles in patients with malignant gliomas through a Phase 2 clinical trial. They compared how peripheral blood mononuclear cell (PBMC) patient profiles varied between receiving standard immunotherapy, autologous tumor lysate dendritic cell vaccination (ATL-DC), with and without adjuvant administration of toll-like receptor (TLR) agonists. They uncovered significant signatures of immune responsiveness and function that accompanied adjuvant therapy. Furthermore, using these observed immune gene signatures, they created an Interferon Activation Score that can serve as a sensitive biomarker for predicted clinical responses to immunotherapy. This score correlated strongly with overall and progression-free survival in patients, reaffirming its potential as a minimally invasive and robust biomarker.
POTENTIAL APPLICATIONS:
- Using Interferon Activation Score to predict patient responsiveness to immunotherapies
- Optimize adjuvant immune-boosting treatments for malignant glioma
ADVANTAGES:
- Standard blood samples to investigate novel biomarkers; No other minimally invasive method exists to predict patient responsiveness to treatments
- Adjuvant immunotherapy with TLR agonists can improve outcomes above standardized immunotherapy
DEVELOPMENT-TO-DATE: UCLA researchers have characterized malignant glioma patient immune responses to standard immunotherapy with adjuvant TLR agonist therapy from Phase II clinical trial. They used this data to develop an Interferon Activation Score that can be obtained with minimal invasive techniques to predict clinical responses to immunotherapy in this patient population.
Related Papers (from the inventors only): Everson, R. G. et al. TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: A randomized phase II trial. Nature Communications 15, (2024).
Technology-related keywords: Malignant glioma, glioblastoma, immunotherapy, biomarker, interferon, adjuvant therapy, chemotherapy, clinical trial, dendritic cell vaccination, immune response