Tumour Immunogen HSP70 Release via Sequential Cooling-Heating

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Solution Overview

Problem

Malignant tumors develop immune tolerance mechanisms to evade immune surveillance, leading to poor treatment outcomes, and current therapies are ineffective in stimulating a robust anti-tumor immune response.

Innovation Solution

A method involving sequential cooling and heating of tumor tissue to specific temperature ranges to promote the release of heat shock protein 70 (HSP70), which activates the immune system by binding to tumor antigens and transforming immunosuppressive cells into mature dendritic cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional thermal therapy is used to treat tumors, then tumor cell necrosis is achieved, but the release of heat shock protein 70 (HSP70) is insufficient to activate robust anti-tumor immune response

Engineering Contradiction:
Improveanti-tumor immune response activationVSAvoidHSP70 release amount
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies periodic thermal action by alternating between cooling phases (to 4°C) and heating phases (to 42-45°C) multiple times. This periodic cool-heat treatment pattern significantly enhances HSP70 release compared to conventional single-phase thermal therapy, thereby activating robust anti-tumor immune response while managing the trade-off between immune activation reliability and HSP70 productivity

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent changes the thermal parameters by introducing temperature cycling between extreme cold (4°C) and hyperthermic ranges (42-45°C), rather than maintaining a constant therapeutic temperature. This parameter variation optimizes both HSP70 release quantity and immune response activation, resolving the contradiction between sufficient HSP70 productivity and reliable immune response

Inventive Principle:
Principle #35Parameter changes

2Reliability

If tumor cells are cooled to very low temperatures to maximize HSP70 release, then immune response activation improves, but tissue damage and cell death increase

Engineering Contradiction:
ImproveHSP70 release efficiencyVSAvoidtissue damage
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The periodic cool-heat cycles allow tissue to recover during heating phases after cooling exposure, reducing cumulative damage while maintaining HSP70 release efficiency. The alternating pattern prevents sustained exposure to damaging extreme temperatures while still achieving the desired immunogenic effect

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The brief cooling periods are followed by warming phases that act as a cushioning recovery period, preventing irreversible tissue damage before it occurs. This anticipatory recovery approach allows the tissue to withstand repeated cooling cycles without excessive damage accumulation

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Reliability

If extended cooling and heating time is used to maximize HSP70 release, then immune response activation improves, but treatment time and patient discomfort increase

Engineering Contradiction:
Improveimmune response activationVSAvoidtreatment duration
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The periodic cool-heat cycles achieve maximum HSP70 release efficiency within each cycle, allowing for optimized treatment protocols that balance immune activation reliability with acceptable treatment duration. The rhythmic nature of the treatment allows for efficient time utilization

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The treatment protocol is made dynamic by adjusting the number of cycles, duration of each phase, and temperature extremes based on individual patient response and tumor type. This dynamic approach optimizes the balance between achieving sufficient immune activation and minimizing treatment time and patient discomfort

Inventive Principle:
Principle #15Dynamics

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 method significantly increases the release of HSP70, enhancing tumor immunity by activating immune responses and improving survival rates in tumor-bearing mice, while also promoting the maturation of immunosuppressive cells into dendritic cells.

Implementation Method 1

cooling the tumor tissue and/or tumor cells to T1, and −50° C.≤T1≤0° C.

Methodology Applied
Scientific EffectCooling: Cooling

Implementation Method 2

heating the cooled tumor tissue and/or tumor cells obtained in I) to T2, and 37° C.≤T2≤60° C.

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 3

A method which combined cool therapy and thermal therapy was used to enhance local tumor cell necrosis, resulting in cell structure disintegration, and releasing a large number of heat shock protein 70 (HSP70)

Methodology Applied
Scientific EffectThermal shock: Thermal Shock

Data Source

PatentUS11396642B2Tumour immunogen, preparation method therefor, and application
Publication Date: 2022.07.26 MAGI CO LTD
  • US11396642B2 patent drawing
  • US11396642B2 patent drawing
  • US11396642B2 patent drawing

AI summary

Provided are a tumour immunogen, a preparation method therefore, and an application. After localised sequential cooling-heating treatment is performed on tumour tissue and/or cells, the tumour tissue and/or cells release a large amount of tumour immunogen heat shock protein 70. The obtained tumour immunogen can activate the body's tumour immune system, to convert immunosuppressive cells into mature dendritic cells, thereby increasing immunogen presentation, and activating tumour immunity.