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Updated: Feb 7, 2026
Ex Vivo Infection of Live Tissue with Oncolytic Viruses
Published on: June 25, 2011
Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency
Marine Ricordel1, Johann Foloppe2, Delphine Antoine3
1Transgene SA, 400 Bld Gonthier d'Andernach, 67400 Illkirch-Graffenstaden, France. mricordel@polyplus-transfection.com.
Abstract:
Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. In this study, we used a directed evolution process, pooling different strains of VACV, including Copenhagen, Western Reserve and Wyeth strains and the attenuated modified vaccinia virus Ankara (MVA), to generate a new recombinant poxvirus with increased oncolytic properties. Through selective pressure, a chimeric VACV, deVV5, with increased cancer cell killing capacity and tumor selectivity in vitro was derived. The chimeric viral genome contains sequences of all parental strains. To further improve the tumor selectivity and anti-tumor activity of deVV5, we generated a thymidine kinase (TK)-deleted chimeric virus armed with the suicide gene FCU1. This TK-deleted virus, deVV5-fcu1 replicated efficiently in human tumor cells, and was notably attenuated in normal primary cells. These studies demonstrate the potential of directed evolution as an efficient way to generate recombinant poxviruses with increased oncolytic potency, and with high therapeutic index to improve cancer therapy.
Insights
Directed evolution created a novel chimeric Vaccinia virus (VACV) with enhanced cancer cell killing ability. Further modification with a suicide gene improved tumor selectivity and anti-tumor activity for improved cancer therapy.
Area of Science:
- Virology
- Oncology
- Genetic Engineering
Background:
- Oncolytic virus (OV) therapy offers a promising, potentially less toxic cancer treatment alternative.
- While Vaccinia virus (VACV)-derived OVs show safety, their monotherapy efficacy can be limited.
- Improving OV potency and tumor selectivity is crucial for enhanced cancer treatment.
Purpose of the Study:
- To generate a novel recombinant poxvirus with enhanced oncolytic properties using directed evolution.
- To improve the tumor selectivity and anti-tumor activity of the derived virus.
- To evaluate the therapeutic potential of engineered viruses for cancer therapy.
Main Methods:
- Directed evolution by pooling different Vaccinia virus strains (Copenhagen, Western Reserve, Wyeth) and MVA.
- Selection under pressure to derive a chimeric VACV (deVV5) with increased in vitro oncolytic potency and tumor selectivity.
- Generation of a thymidine kinase (TK)-deleted chimeric virus (deVV5-fcu1) armed with the suicide gene FCU1.
Main Results:
- A chimeric VACV, deVV5, was successfully generated with enhanced cancer cell killing capacity and tumor selectivity.
- The TK-deleted deVV5-fcu1 virus demonstrated efficient replication in human tumor cells.
- deVV5-fcu1 showed significant attenuation in normal primary cells, indicating improved safety.
Conclusions:
- Directed evolution is an effective strategy for generating recombinant poxviruses with superior oncolytic potency.
- The engineered virus deVV5-fcu1 exhibits enhanced tumor selectivity and replication efficiency.
- These findings highlight the potential of engineered OVs with a high therapeutic index to advance cancer therapy.
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