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Updated: Oct 8, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Protocols to Manufacture an Oncolytic Measles Virus-Sensitive Immunocompetent Mouse Model of Medulloblastoma
1Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. sangeet.lal@ucsf.edu.
Abstract:
Oncolytic virotherapy translational research in the current era is heavily focused on the interaction of the immune system and tumor microenvironment with oncolytic viruses. Preclinical xenograft studies using human cells in immunodeficient mouse models does not serve this purpose. As a consequence, developing syngeneic immunocompetent murine cancer models sensitive to infection and growth of specific oncolytic viruses is required. The group 3 subtype of medulloblastoma, among the four molecular subgroups-WNT, SHH, Group 3, and Group 4, has the worst prognosis and the poorest outcome. Sadly, current treatments cause long-term toxicity and morbidity to survivors adversely affecting their quality of life. Alternate effective therapy with less side effects is urgently needed. We have shown that oncolytic measles virus (MV) is effective against localized as well as CSF-disseminated medulloblastoma in immunodeficient mouse models. To study the interaction of immune system with oncolytic measles virotherapy, we have developed a murine group 3 medulloblastoma cell line (CSCG) that is infectible by MV, is killed by MV, allows replication of MV, and is tumorigenic in the brain of syngeneic transgenic immune-competent mice. Intratumoral injection of MV results in significant prolongation of survival in mice bearing CSCG tumors in the brain. This model provides the first suitable platform to examine therapeutic regimens of MV therapy for MB tumors in the presence of intact immune system. Here, we describe our lab protocols to develop this cell line and the mouse model.
Insights
Researchers developed a new immunocompetent mouse model for studying oncolytic measles virus (MV) therapy in Group 3 medulloblastoma. This model enables investigation of MV's interaction with the immune system for improved cancer treatment.
Area of Science:
- Oncology
- Virology
- Immunology
- Genetics
Background:
- Oncolytic virotherapy research emphasizes immune system and tumor microenvironment interactions.
- Current preclinical models using immunodeficient mice do not adequately represent these interactions.
- Group 3 medulloblastoma has a poor prognosis, and existing treatments cause significant long-term toxicity.
Purpose of the Study:
- To develop a syngeneic, immunocompetent murine model for studying oncolytic measles virus (MV) in Group 3 medulloblastoma.
- To establish a platform for investigating MV therapy in the context of an intact immune system.
- To provide a suitable model for evaluating therapeutic regimens of MV for medulloblastoma.
Main Methods:
- Development of a murine Group 3 medulloblastoma cell line (CSCG) susceptible to MV infection, replication, and cell killing.
- Establishment of a syngeneic, immunocompetent mouse model using CSCG cells implanted in the brain.
- Administration of intratumoral MV injection in tumor-bearing mice.
Main Results:
- The developed CSCG cell line is infectible by, killed by, and supports replication of MV.
- CSCG cells are tumorigenic in the brain of syngeneic immunocompetent mice.
- Intratumoral MV injection significantly prolonged survival in mice with brain CSCG tumors.
Conclusions:
- A novel immunocompetent murine model for Group 3 medulloblastoma has been established.
- This model is suitable for studying oncolytic measles virus (MV) therapy in the presence of an intact immune system.
- The model facilitates the examination of MV's interaction with the tumor microenvironment and immune responses, paving the way for improved therapeutic strategies.
