NKT-like Cell Expansion Using Allogeneic Somatic Cells

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Solution Overview

Problem

Current methods for activating and expanding CD8+ NKT-like cells in vitro are inefficient and require the addition of cytokines, limiting large-scale expansion and activation of these cells, which are crucial for their antitumor effects.

Innovation Solution

A method involving co-culture of lymphocytes from a first subject with nucleated somatic cells from a second allogeneic or heterogeneous subject, expressing immune co-stimulatory molecules, to expand CD8+ NKT-like cells by 10 to 1000 times, without the need for cytokine addition, and enhance their activation markers and killing effector molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cytokines are added to expand NKT-like cells, then cell activation and expansion can be achieved, but the process becomes complex and limits large-scale expansion

Engineering Contradiction:
Improvecell expansion capabilityVSAvoidculture process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts and removes the requirement for cytokine addition from the cell expansion process. By using allogeneic nucleated somatic cells as a natural stimulator, the method eliminates the need for external cytokine supplementation, thereby simplifying the culture process while maintaining effective NKT-like cell expansion and activation

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The allogeneic nucleated somatic cells naturally provide the necessary co-stimulatory signals and cytokines through their inherent biological functions. The system becomes self-sufficient, where the somatic cells themselves generate the required biological environment for NKT-like cell expansion without external intervention, reducing process complexity

Inventive Principle:
Principle #25Self-service

2Quantity of substance

If current activation methods are used, then some cell expansion is achieved, but large-scale expansion is limited

Engineering Contradiction:
Improvecell numberVSAvoidexpansion efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent performs preliminary action by pre-preparing allogeneic nucleated somatic cells before the actual NKT-like cell expansion. These somatic cells are cultured and characterized in advance to ensure they possess the necessary co-stimulatory properties, enabling them to effectively drive large-scale NKT-like cell expansion when introduced to the lymphocyte culture

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The allogeneic nucleated somatic cells serve as an intermediary that mediates the expansion of NKT-like cells. Rather than directly stimulating NKT-like cells with complex cytokine mixtures, the somatic cells act as a natural bridge, providing physiological co-stimulatory signals that result in more efficient and scalable cell expansion

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This method simplifies and enhances the expansion and activation of CD8+ NKT-like cells, increasing their antitumor effects by significantly increasing cell numbers and expression of activation markers like CD25, CD44, CD69, Granzyme B, and Perforin.

Implementation Method 1

nucleated somatic cells from a second allogeneic or heterogeneous subject, expressing immune co-stimulatory molecules

Methodology Applied
Scientific EffectImmune co-stimulatory molecule interaction:

Data Source

PatentUS10443041B2Method for activating and expanding NKT-like cells in vitro
Publication Date: 2019.10.15 BEIJING ZHONGTAI HENGJI BIOLOGICAL TECH CO LTD
  • US10443041B2 patent drawing
  • US10443041B2 patent drawing
  • US10443041B2 patent drawing

AI summary

The invention relates to a method for activating and expanding NKT-like cells in vitro. The method according to the present invention utilizes nucleated somatic cells derived from allogeneic or heterologous subjects to activate and proliferate NKT-like cells of a subject in vitro, and can increase the overall number of the NKT-like cells, the expression of activation markers and the number of killing effector molecules.