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Updated: Oct 5, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Robust envelope exchange platform for oncolytic measles virus
S Neault1, S Bossow2, C Achard3
1Ottawa Hospital Research Institute, Cancer Therapeutics Program, 501 Smyth Road, Ottawa, Ontario, Canada; University of Ottawa, Faculty of Medicine, 451 Smyth Rd, Ottawa, Ontario, Canada.
Abstract:
The use of oncolytic viruses (OV) to precisely target and eliminate tumors ('virotherapy') is a rapidly evolving therapeutic approach to treating cancer. A major obstacle in virotherapy, especially for systemic administration, is the host's immune response towards the OV. In the case of measles virus (MeV), most individuals have been immunized against this agent leading to pre-existing neutralizing antibodies that can impair OV delivery to the tumor. These antibodies predominantly target the hemagglutinin (H) and fusion (F) envelope glycoproteins displayed at the particle's surface. Here, we introduce a novel and versatile pseudotyping platform for rapid envelope exchange of oncolytic MeV that allows for engineering of chimeric viruses invulnerable to pre-existing anti-MeV antibodies. Using this system, we have successfully exchanged the MeV F and H proteins with the glycoprotein G of vesicular stomatitis virus (VSV) and the surface proteins of Newcastle disease virus (NDV) or canine distemper virus (CDV), all of which are not endemic in the general human population. While the MeV-VSV and MeV-NDV pseudotypes were non-functional, the MeV-CDV pseudotype was successfully propagated to high-titer virus stocks. This study describes the successful generation of a robust envelope exchange platform for oncolytic MeV while also highlighting its intricate pseudotyping tolerance.
Insights
This study developed a platform to engineer oncolytic measles viruses (MeV) resistant to pre-existing antibodies. A chimeric MeV using canine distemper virus (CDV) envelope proteins successfully overcame immune barriers for potential cancer virotherapy.
Area of Science:
- Oncolytic virotherapy
- Viral immunology
- Molecular virology
Background:
- Oncolytic viruses (OV) offer a promising cancer treatment strategy.
- Pre-existing immunity, particularly neutralizing antibodies against measles virus (MeV), hinders OV efficacy.
- Antibodies target MeV envelope glycoproteins (hemagglutinin and fusion proteins).
Purpose of the Study:
- To engineer oncolytic MeV resistant to pre-existing anti-MeV antibodies.
- To develop a versatile platform for rapid envelope exchange in MeV.
- To create chimeric MeV with altered surface glycoproteins for immune evasion.
Main Methods:
- Developed a novel pseudotyping platform for MeV envelope exchange.
- Exchanged MeV F and H proteins with glycoproteins from vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and canine distemper virus (CDV).
- Assessed the functionality and propagation of engineered chimeric MeV.
Main Results:
- Successfully generated a platform for rapid MeV envelope exchange.
- Engineered MeV-VSV and MeV-NDV pseudotypes were non-functional.
- An MeV-CDV pseudotype was successfully propagated to high titers, demonstrating functionality.
- Highlighted the platform's pseudotyping tolerance and limitations.
Conclusions:
- A robust platform for engineering immune-evasive oncolytic MeV was established.
- Chimeric MeV expressing CDV envelope proteins show potential for overcoming anti-MeV immunity.
- Further research is needed to optimize pseudotyping and assess therapeutic efficacy.
