Chimeric Poxvirus Engineering for Tumor-Selective Oncolysis
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Solution Overview
Problem
Current oncolytic poxviruses lack sufficient oncolytic power to infect and lyse all tumor cells, are limited by physical barriers within the tumor microenvironment, and can be neutralized by the host immune system, leading to reduced therapeutic efficacy and safety concerns.
Innovation Solution
Development of chimeric poxviruses through a directed evolution method using a mix of sixteen strains, including Rabbitpox and Vaccinia viruses, with specific genetic modifications to enhance oncolytic properties, EEV-secretion capacity, and tumor selectivity, and the ability to encode transgenes like IL-12.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current oncolytic poxviruses are used to treat cancer, then they can infect and lyse some tumor cells, but they lack sufficient oncolytic power to infect and lyse all tumor cells
Solution Approach 1:
The patent combines multiple poxvirus strains (including Vaccinia, Cowpox, and Rabbitpox viruses) into chimeric poxviruses through genetic recombination. This merging of different viral strains integrates their respective advantageous properties, resulting in chimeric viruses with enhanced oncolytic power that can effectively infect and lyse all tumor cells while maintaining safety
2Ease of operation
If oncolytic poxviruses are administered systemically, then they can reach tumors throughout the body, but they are limited by physical barriers within the tumor microenvironment
Solution Approach 1:
The patent modifies key viral parameters including enhancing EEV-secretion capacity and altering surface proteins of the chimeric poxviruses. These parameter changes enable the viruses to better navigate through physical barriers in the tumor microenvironment, improving intratumoral spread while maintaining systemic deliverability
3Productivity
If oncolytic poxviruses are used to treat cancer, then they can kill cancer cells, but they can be neutralized by the host immune system, leading to reduced therapeutic efficacy
Solution Approach 1:
The patent creates chimeric poxviruses with locally optimized properties by incorporating genes from different poxvirus strains that confer resistance to specific immune mechanisms. The viruses express localized modifications in their protein structures that reduce recognition by host antibodies and immune cells, thereby maintaining high cancer cell killing capacity while evading immune neutralization
4Productivity
If oncolytic poxviruses are used to treat cancer, then they can provide therapeutic benefits, but safety concerns arise from their virulence and potential impact on healthy cells
Solution Approach 1:
The patent segments the genome of different poxvirus strains and selectively combines only the beneficial oncogenic and oncolytic genes while excluding virulence factors that could harm healthy cells. This segmented approach allows creation of chimeric viruses with high therapeutic efficacy but reduced safety risks compared to parental strains
Data Source
AI summary
The present invention relates to a chimeric poxvirus with improved anticancer activity (higher cancer cell killing capacities and better tumor selectivity), as well as variant version thereof with one or more altered viral genes, recombinant versions thereof comprise one or more nucleic acid(s) of interest and recombinant variant versions thereof, all of which may be included in a composition and used for the treatment of a disease, in particular proliferative disease, notably cancers.