Oncolytic MYXV Therapy to Convert Nonpermissive Tumor Cells

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Solution Overview

Problem

Oncolytic viruses face limitations in infecting nonpermissive or semi-permissive tumor cells, reducing their therapeutic efficacy.

Innovation Solution

Administering a myxoma virus (MYXV) in combination with a nuclear export inhibitor, such as selinexor, to enhance viral replication and gene expression in cancer cells, thereby converting non-permissive cells into permissive ones and promoting cancer cell killing and immune activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If oncolytic viruses are used to treat cancer, then immune activation and cancer cell killing occur, but the viruses cannot effectively infect nonpermissive or semi-permissive tumor cells

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidability to infect different tumor cell types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the nuclear export status parameter of cancer cells by administering nuclear export inhibitors (such as selinexor, leptomycin B, or KPT-330) to block CRM1-mediated nuclear export. This parameter change converts nonpermissive or semi-permissive tumor cells into permissive cells, enabling effective oncolytic virus infection and replication while maintaining the virus's ability to selectively target cancer cells over normal cells.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If nuclear export is inhibited to enhance viral replication, then viral replication increases, but nuclear export is a fundamental cellular process that could have side effects

Engineering Contradiction:

Improveviral replicationVSAvoidpotential side effects from inhibiting nuclear export

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by administering the nuclear export inhibitor before or concurrently with the oncolytic virus to pre-condition the cancer cells. This preliminary inhibition of nuclear export creates a permissive environment that enhances subsequent viral replication while limiting the duration and scope of the inhibitor's exposure, thereby reducing potential side effects.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The nuclear export inhibitor acts as an intermediary that temporarily modifies the cellular environment to facilitate viral replication. By using a small molecule inhibitor as a mediator between the therapeutic goal (enhanced viral replication) and the biological system, the patent achieves the desired effect while the inhibitor can be carefully controlled in terms of dosage, timing, and duration to minimize harmful effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If combination therapy with nuclear export inhibitor and oncolytic virus is used, then cancer load reduction increases, but treatment complexity increases

Engineering Contradiction:

Improvecancer load reductionVSAvoidtreatment regimen complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the treatment into two distinct functional components: (1) a nuclear export inhibitor administered orally or systemically to modify cellular permissiveness, and (2) an oncolytic virus administered locally or systemically to execute the therapeutic killing function. This segmentation allows each component to be optimized independently and simplifies the overall treatment protocol compared to developing a completely new monotherapy.

Inventive Principle:

Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combination therapy significantly increases MYXV replication by at least 10% and reduces cancer load and metastasis by at least 10%, while prolonging survival by at least 5% compared to treatments without the inhibitor.

Implementation Method 1

the nuclear export inhibitor binds to and/or inhibits exportin 1 (XPO1/CRM1)

Methodology Applied

Scientific EffectNuclear export inhibition:

Implementation Method 2

Oncolytic viruses, such as from the Poxviridae family of viruses, can be mammalian viruses that are designed and/or selected for their ability to selectively infect and kill transformed cancer cells

Methodology Applied

Scientific EffectViral infection and replication:

Data Source

PatentUS20250249056A1Cancer therapies comprising a nuclear export inhibitor and an oncolytic virus

Publication Date: 2025.08.07 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA

AI summary

Disclosed herein are compositions and methods for treating cancer. The methods can comprise administrating to a subject with cancer a therapeutically effective amount of an oncolytic virus and a therapeutically-effective amount of a nuclear export inhibitor. Methods disclosed herein can convert nonpermissive or semi-permissive cancers to permissive cancers that are susceptible to infection and killing by oncolytic viruses.