MAVS Protein Overexpression for Refractory Tumor Immunosuppression

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Solution Overview

Problem

Many tumors remain refractory to current cancer immunotherapies due to their highly immunosuppressive microenvironment, particularly evident in colorectal carcinomas where ~90% are unresponsive to immune checkpoint blockade.

Innovation Solution

Overexpressing the Mitochondrial Antiviral Signaling protein (MAVS) in cancerous and non-cancerous cells to activate innate immune signaling, leading to robust inflammatory signaling that alters the tumor microenvironment to suppress tumor growth and stimulate anti-tumor immune responses, potentially combined with other anti-cancer therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immune checkpoint blockade is used to treat cancer, then adaptive immune response is enhanced, but tumors with immunosuppressive microenvironment remain refractory

Engineering Contradiction:

Improveefficacy of immune checkpoint blockadeVSAvoidimmunosuppressive microenvironment

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by overexpressing MAVS in tumor cells before administering immune checkpoint blockade therapy. This pre-activation of innate immune signaling pathways (RIG-I/MAVS) creates a more favorable microenvironment that primes the tumor for subsequent adaptive immune response, making the checkpoint blockade effective where it would otherwise fail.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses MAVS overexpression as an intermediary mechanism to bridge the gap between innate and adaptive immunity. By activating MAVS-mediated type I interferon production and inflammatory signaling, it creates an intermediate state that converts the immunosuppressive microenvironment into an immunostimulatory one, enabling immune checkpoint blockade to work.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If MAVS is overexpressed to activate innate immune signaling, then type I interferons and cytokine production increase, but tumor microenvironment must be sufficiently altered to suppress tumor growth

Engineering Contradiction:

Improvetype I interferons and cytokine productionVSAvoidtumor growth suppression

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies parameter changes by modulating the expression level of MAVS in tumor cells. By controlling the degree of MAVS overexpression, it optimizes the production of type I interferons and cytokines to achieve sufficient microenvironment alteration for tumor growth suppression while avoiding excessive inflammation that could have harmful effects.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11224665B2Mitochondrial antiviral signaling (MAVS) protein compositions and methods of using the same

Publication Date: 2022.01.18 DUKE UNIV

AI summary

The invention generally relates to compositions and methods for preventing and treating cancer. More specifically, the invention relates to MAVS compositions and their use in cancer therapeutics that may be used to treat various cancers alone or in combination with other anti-cancer therapeutic agents.