Fusogenic Oncolytic Virus Platform for Stronger Anti-Tumor Immunity

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing oncolytic therapies using viruses, such as herpes simplex virus (HSV), do not effectively induce immune responses in all tumors and patients, leading to variable treatment outcomes, and there is a need for improved direct oncolytic effects and immune stimulation to enhance anti-tumor responses.

Innovation Solution

Oncolytic viruses engineered to express a fusogenic protein and immune stimulatory molecules, such as GM-CSF or GITRL, to enhance tumor antigen release and immune response, combined with immune checkpoint blockade or IDO inhibitors for synergistic anti-tumor effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional oncolytic viruses are used, then tumor cells are killed directly, but immune response induction is insufficient and variable

Engineering Contradiction:

Improvetreatment efficacyVSAvoidimmune response deficiency

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent combines multiple functions into a single oncolytic virus platform: direct oncolysis through viral replication, immune stimulation through cytokine expression (GM-CSF, IL-12, IFN-alpha), and immune modulation through checkpoint inhibitor expression (anti-CTLA-4, anti-PD-1). This merging of functions ensures reliable and potent anti-tumor immunity while maintaining direct tumor cell killing.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The oncolytic virus is engineered as a composite therapeutic agent containing multiple transgenes that encode different functional proteins. This composite structure allows simultaneous expression of oncolytic enzymes, immunostimulatory cytokines, and immune checkpoint inhibitors, creating a multi-functional therapeutic with enhanced and consistent efficacy.

Inventive Principle:

Principle #40Composite materials

2Productivity

If virus replication is enhanced in tumors, then direct oncolytic effects are improved, but selectivity against normal tissue must be maintained

Engineering Contradiction:

Improveviral replication efficiencyVSAvoidnormal tissue damage

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The oncolytic virus is engineered with tumor-selective replication properties through mutations in viral genes (e.g., ICP34.5, ICP47 in HSV-1) that restrict replication to tumor cells with specific metabolic or signaling characteristics. This allows high viral replication efficiency in tumors while maintaining selectivity and avoiding damage to normal tissues.

Inventive Principle:

Principle #3Local quality

3Reliability

If multiple immune stimulatory molecules are expressed, then immune response is enhanced, but device complexity increases

Engineering Contradiction:

Improveimmune response potencyVSAvoidvirus engineering complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The oncolytic virus platform is designed as a universal multi-functional system that can simultaneously express multiple immune stimulatory molecules (cytokines, checkpoint inhibitors, costimulatory ligands) from a single viral genome. This universal platform approach standardizes the complex engineering while enabling flexible combination of different immune-modulating components.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS12465639B2Modified oncolytic virus

Publication Date: 2025.11.11 REPLIMUNE

AI summary

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene and (ii) an immune stimulatory molecule-encoding gene.