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Updated: Jul 5, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial
Evanthia Galanis1,2, Katharine E Dooley3, S Keith Anderson3
1Department of Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA. galanis.evanthia@mayo.edu.
Abstract:
Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was safety and toxicity: treatment was well tolerated with no dose-limiting toxicity being observed up to the maximum feasible dose (2×107 TCID50). Median OS, a secondary endpoint, was 11.6 mo and one year survival was 45.5% comparing favorably with contemporary controls. Other secondary endpoints included assessment of viremia, MV replication and shedding, humoral and cellular immune response to the injected virus. A 22 interferon stimulated gene (ISG) diagonal linear discriminate analysis (DLDA) classification algorithm in a post-hoc analysis was found to be inversely (R = -0.6, p = 0.04) correlated with viral replication and tumor microenvironment remodeling including proinflammatory changes and CD8 + T cell infiltration in post treatment samples. This data supports that oncolytic MV derivatives warrant further clinical investigation and that an ISG-based DLDA algorithm can provide the basis for treatment personalization.
Insights
Oncolytic measles virus (MV) derivatives show promise for treating glioblastoma (GBM). This trial found the MV-CEA treatment safe and well-tolerated, with encouraging survival rates and potential for personalized treatment strategies.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Glioblastoma (GBM) is the most aggressive brain tumor with limited treatment options.
- Measles virus (MV) vaccine strains exhibit preclinical antitumor effects against GBM.
- Oncolytic viruses are engineered to selectively infect and kill cancer cells.
Purpose of the Study:
- To evaluate the safety and efficacy of an oncolytic measles virus derivative (MV-CEA) in patients with recurrent GBM.
- To assess the correlation between viral replication, immune response, and clinical outcomes.
- To explore potential biomarkers for treatment response.
Main Methods:
- A Phase I clinical trial involving 22 recurrent GBM patients.
- Administration of MV-CEA via resection cavity or intratumoral injection.
- Monitoring of safety, toxicity, overall survival (OS), viremia, and immune responses.
- Post-hoc analysis using a 22 interferon-stimulated gene (ISG) algorithm to correlate with viral activity and tumor microenvironment.
Main Results:
- MV-CEA was well-tolerated up to the maximum feasible dose, with no dose-limiting toxicity observed.
- Median OS was 11.6 months, with a 1-year survival rate of 45.5%, comparing favorably to controls.
- A significant inverse correlation was found between an ISG-based algorithm and viral replication, indicating tumor microenvironment remodeling.
Conclusions:
- Oncolytic MV derivatives, like MV-CEA, warrant further clinical investigation for GBM treatment.
- The ISG-based DLDA algorithm shows potential as a predictive biomarker for treatment response and personalization.
- The study supports the potential of oncolytic virotherapy in modifying the tumor immune microenvironment.
