Oncolytic Virus Delivery of CD47/SIRP-Alpha Checkpoint Inhibitors

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Solution Overview

Problem

Cancer treatments face challenges in achieving targeted biologic delivery to tumor sites and overcoming immune evasion mechanisms employed by tumor cells, which reduce the effectiveness of cancer immunotherapies.

Innovation Solution

Compositions comprising oncolytic viruses engineered to express soluble SIRP-alpha polypeptides or anti-CD47 antibodies, disrupting the CD47/SIRP-alpha immune checkpoint to enhance macrophage response and activate anti-tumor immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cancer immunotherapies are used, then immune response against tumor cells is activated, but tumor cells employ immune evasion mechanisms that reduce treatment effectiveness

Engineering Contradiction:

Improveeffectiveness of cancer immunotherapyVSAvoidimmune evasion by tumor cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces soluble SIRP-alpha polypeptide as an intermediary that binds to CD47 on tumor cells, blocking the CD47/SIRP-alpha immune checkpoint interaction. This mediator prevents tumor cells from sending 'don't eat me' signals to macrophages, thereby enhancing macrophage-mediated tumor cell recognition and destruction while overcoming tumor immune evasion mechanisms

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the immune checkpoint parameters by introducing soluble SIRP-alpha that alters the binding dynamics between CD47 and membrane-bound SIRP-alpha. By changing the physical-chemical state of the immune checkpoint interaction (from membrane-bound to soluble), the therapy enhances macrophage activity and overcomes tumor cell immune evasion

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If targeted biologic delivery to tumor sites is attempted, then treatment specificity is improved, but delivery challenges and local expression stability issues persist

Engineering Contradiction:

Improvespecificity to target locationsVSAvoidlocal expression stability

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The oncolytic virus is engineered to autonomously express the soluble SIRP-alpha polypeptide directly at the tumor site after infection. The virus self-delivers the therapeutic gene and the infected tumor cells become factories for producing the immune checkpoint inhibitor locally, eliminating the need for complex external delivery systems and ensuring stable local expression

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The oncolytic virus is designed to first infect and replicate in tumor cells, establishing presence and initiating gene expression before the therapeutic effect fully manifests. This preliminary viral replication ensures localized delivery and expression stability by using the tumor cell machinery to produce the soluble SIRP-alpha polypeptide in situ

Inventive Principle:

Principle #10Preliminary action

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

Enhances immune response against tumor cells by blocking the CD47/SIRP-alpha interaction, increasing macrophage activity and reducing tumor growth incidence.

Implementation Method 1

soluble SIRP-alpha polypeptide or functional fragment thereof... blocking the CD47/SIRP-alpha interaction

Methodology Applied

Scientific EffectProtein-protein binding:

Implementation Method 2

sequence encoding for an anti-CD47 antibody or fragment thereof... disrupting the CD47/SIRP-alpha immune checkpoint

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 3

an oncolytic virus comprising an exogenous nucleic acid... reducing tumor growth incidence

Methodology Applied

Scientific EffectOncolytic viral lysis:

Data Source

PatentUS20250302899A1Compositions of CD47/SIRP-alpha immune checkpoint inhibitors and uses thereof

Publication Date: 2025.10.02 KALIVIR IMMUNOTHERAPEUTICS INC

AI summary

The present disclosure provides for an oncolytic virus comprising an exogenous nucleic acid encoding for a polypeptide that acts as a CD47-SIRP-alpha immune checkpoint inhibitor. Oncolytic viruses optionally comprise a mutation or deletion of the gene expressing IFN-gamma. Compositions described herein are further described for use in the treatment of cancer.