Immunogenic Extracellular Vesicles via ER Stress Inducers

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Solution Overview

Problem

Existing technologies lack effective methods for separating and purifying extracellular vesicles with enhanced immunogenicity from tumor cells, and there is a limited understanding of the mechanisms regulating their immunogenicity, hindering the development of innovative cancer treatment strategies.

Innovation Solution

The production of extracellular vesicles from tumor cells cultured in an environment with an endoplasmic reticulum stress inducer, such as tunicamycin, increases immune-activating proteins and decreases immune-suppressive proteins, enhancing their immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If tumor cells are cultured without endoplasmic reticulum stress inducer, then the production process is simple, but the extracellular vesicles have low immunogenicity with insufficient immune-activating proteins and high immune-suppressive proteins

Engineering Contradiction:

Improveimmunogenicity of extracellular vesiclesVSAvoidcomplexity of culture process

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by introducing endoplasmic reticulum stress inducers (such as tunicamycin, 2-deoxy-D-glucose, brefeldin A, or thapsigargin) into the tumor cell culture medium at specific concentrations (e.g., 0.01-10 μg/mL for tunicamycin, 1-100 μM for 2-deoxy-D-glucose). This chemical parameter modification triggers the unfolded protein response pathway, leading to increased immune-activating proteins (HMGB1, HSP70) and decreased immune-suppressive proteins in the secreted extracellular vesicles, thereby enhancing their immunogenicity without requiring complex device modifications

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses endoplasmic reticulum stress inducers as intermediary substances that mediate the transformation of ordinary tumor cell-derived extracellular vesicles into immunogenic ones. These inducers act as chemical mediators that trigger intracellular stress response pathways, which in turn modify the protein composition of secreted vesicles. The intermediaries enable the conversion process without direct manipulation of the vesicles themselves, simplifying the overall process while achieving the desired immunogenicity enhancement

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If tumor cells are treated with endoplasmic reticulum stress inducer, then immune-activating proteins increase and immune-suppressive proteins decrease, but the production cost and process complexity increase

Engineering Contradiction:

Improvecancer treatment effectVSAvoidease of production

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-treating tumor cells with endoplasmic reticulum stress inducers during the culture phase before harvesting the extracellular vesicles. This preliminary modification of the parent cells ensures that the secreted vesicles are pre-loaded with enhanced immunogenic components (increased HMGB1, HSP70 and decreased immune-suppressive proteins). By performing the immunogenicity enhancement step in advance during cell culture, the patent eliminates the need for complex post-processing modifications, thereby maintaining ease of manufacture while achieving superior cancer treatment effects

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent modifies cultural parameters by controlling the concentration, treatment duration, and type of endoplasmic reticulum stress inducer to optimize the balance between production efficiency and immunogenicity enhancement. Specific parameter ranges are established (e.g., tunicamycin at 0.01-10 μg/mL for 24-72 hours) to achieve the desired protein composition changes without excessive complexity or cost, making the production process economically viable while ensuring effective cancer treatment outcomes

Inventive Principle:

Principle #35Parameter changes

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 resulting composition of immunogenic tumor-derived extracellular vesicles demonstrates excellent cancer treatment effects by stimulating immune responses against cancer cells.

Implementation Method 1

tumor cells treated with an endoplasmic reticulum stress inducer to increase immune-activating protein and decrease immune-suppressive protein

Methodology Applied

Scientific EffectEndoplasmic reticulum stress:

Implementation Method 2

when tumor cells are treated with an endoplasmic reticulum stress inducer, they secrete extracellular vesicles with enhanced immunogenicity

Methodology Applied

Scientific EffectUnfolded protein response:

Data Source

PatentUS20250134926A1Composition for Anti-cancer treatment comprising immunogenic tumor-derived extracellular vesicles using an endoplasmic reticulum stress inducer and method for producing the same

Publication Date: 2025.05.01 RES & BUSINESS FOUND SUNGKYUNKWAN UNIV

AI summary

The present invention relates to a composition for anti-cancer treatment, the composition including immunogenic tumor-derived extracellular vesicles using an endoplasmic reticulum stress inducer, and a method for producing the same. The composition according to the present invention includes extracellular vesicles in which tumor immune-activating protein is increased and immune-suppressive protein is decreased so that immunogenicity is enhanced, and thus can be used as a pharmaceutical composition or a food composition for anti-cancer treatment.