Chimeric HSV Vector With IL-21 Expression for Variable Tumor Response

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Solution Overview

Problem

Existing oncolytic herpes simplex viruses (oHSVs) face challenges in effectively targeting and stimulating antitumor immunity due to variations in tumor permissivity and stromal and immune cell composition, leading to suboptimal therapeutic benefits in certain cancers.

Innovation Solution

A non-natural herpes simplex virus (HSV) vector is engineered to express IL-21, with the IL-21 polynucleotide inserted at the ICP34.5 locus and under the control of a modified retroviral promoter, enhancing cytokine production and immune-mediated anti-tumor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional oncolytic HSV is used, then virus spread occurs, but the spread is intrinsically slow in some cancers leading to suboptimal therapeutic benefit

Engineering Contradiction:

Improvevirus spread speedVSAvoidtherapeutic benefit

Core Design Contradiction:

SpeedVSReliability

Solution Approach 1:

The patent introduces IL-21 cytokine expression into the oncolytic HSV vector before administration, preparing the immune system in advance to respond more rapidly and effectively when the virus infects tumor cells, thereby accelerating the overall therapeutic effect without waiting for slow natural virus spread

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent modifies the viral vector by inserting IL-21 polynucleotide sequences into the HSV genome at specific loci (ICP34.5 or RL1/g134.5), changing the biological parameters of the virus to enhance immune stimulation and improve therapeutic efficacy in cancers with slow virus spread

Inventive Principle:

Principle #35Parameter changes

2Productivity

If oncolytic HSV is used, then direct infection and lysis of cells occurs, but variations in tumor permissivity lead to inconsistent therapeutic responses

Engineering Contradiction:

Improvecell lysis efficiencyVSAvoidtumor permissivity variation

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent equips the oncolytic HSV with dual functionality: maintaining its original lytic activity while simultaneously expressing IL-21 cytokine. This multi-functionality allows the virus to effectively treat diverse tumor types with varying permissivity levels by providing both direct cell killing and immune-mediated anti-tumor activity

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If oncolytic HSV is used, then stimulation of antitumor immunity occurs, but variations in stromal and immune cell composition lead to variations in immune reaction capacity

Engineering Contradiction:

Improveimmune reaction consistencyVSAvoidimmune cell composition variation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the immune microenvironment parameters by introducing IL-21, a cytokine that potently activates and expands CD8+ T cells and NK cells. This parameter change compensates for variations in native immune cell composition and stromal factors, creating a more consistent and robust anti-tumor immune response across different tumor types

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The IL-21 cytokine acts as an intermediary substance that bridges the gap between viral infection and immune activation. It mediates the interaction between the oncolytic virus and the host immune system, enhancing immune cell function independently of variations in tumor stromal composition

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250295718A1Chimeric HSV expressing hil21 to boost Anti-tumor immune activity

Publication Date: 2025.09.25 RES INST AT NATIONWIDE CHILDRENS HOSPITAL

AI summary

Provided herein are non-natural herpes simplex virus (“HSV”) vectors and one or more polynucleotides encoding IL-21 or a biologically active fragment of IL-21 for use in the treatment of cancer.