Balanced Immune Cell Culture via Anti-CD16 and Anti-CD3 Segmentation

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Solution Overview

Problem

Conventional cellular immunotherapy methods fail to enhance immunocompetence by only differentiating mononuclear cells into a single type of immune cell, such as cytotoxic T cells, rather than achieving a well-balanced differentiation into multiple types like NK cells, NKT cells, and T cells.

Innovation Solution

A method involving specific cell culture steps using a culture medium with anti-CD16 monoclonal antibody and IL-2 or IL-15 to differentiate mononuclear cells into NK cells and NKT cells, followed by culturing in the presence of anti-CD3 antibody to preferentially stimulate cytotoxic T cells, ensuring a balanced proliferation of immune cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mononuclear cells are differentiated into a single type of immune cell (e.g., cytotoxic T cells) as in conventional cellular immunotherapy, then the differentiation process is simple and focused, but immunocompetence in vivo is not necessarily enhanced and the immune response is insufficient

Engineering Contradiction:
Improveimmunocompetence enhancementVSAvoidcell culture process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The cell culture process is segmented into distinct phases: a first culture phase using anti-CD16 monoclonal antibody and IL-2/IL-15 to generate NK cells and NKT cells, followed by a second culture phase using anti-CD3 antibody to expand T cells. This segmentation allows each phase to target specific immune cell types, ensuring comprehensive immunocompetence enhancement while maintaining manageable process complexity through structured methodology

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes cultural parameters (antibody types, cytokine combinations, culture conditions) between phases to direct differentiation toward multiple immune cell types. By adjusting these parameters systematically, the process achieves reliable immunocompetence enhancement through balanced production of NK cells, NKT cells, and T cells without requiring overly complex procedures

Inventive Principle:
Principle #35Parameter changes

2Reliability

If multiple types of immune cells are differentiated in a well-balanced manner, then immunocompetence is effectively enhanced, but the culture conditions and process control become more complex

Engineering Contradiction:
Improveimmunocompetence enhancementVSAvoidculture process ease of operation
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The culture process is designed as a dynamic two-phase system where conditions are adjusted at specific transitions. The first phase dynamically generates NK and NKT cells under anti-CD16/IL-2 or IL-15 conditions, then transitions to the second phase for T cell expansion under anti-CD3 conditions. This dynamic approach enables balanced multi-type immune cell production while maintaining operational ease through clear phase transitions and standardized protocols

Inventive Principle:
Principle #15Dynamics

3Productivity

If conventional single-type immune cell therapy is used, then the treatment protocol is simpler, but the therapeutic effect is limited and may not sufficiently enhance patient immunocompetence

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidmanufacturing process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention merges multiple immune cell types (NK cells, NKT cells, and T cells) into a single therapeutic product through a coordinated two-phase culture process. The first phase merges NK and NKT cell generation, while the second phase merges T cell expansion, creating a comprehensive immunotherapy product that delivers enhanced therapeutic effectiveness despite the increased manufacturing process complexity

Inventive Principle:
Principle #5Merging (Combining)

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 efficiently differentiates and proliferates mononuclear cells into NK cells, NKT cells, and T cells in a well-balanced manner, reducing the burden on patients by requiring less blood volume and minimizing the need for multiple apheresis procedures, while maintaining cellular cytotoxicity and antitumor activity.

Implementation Method 1

culturing mononuclear cells in a culture medium containing anti-CD16 monoclonal antibody and any one of IL-2, IL-15 or IL-2 and IL-15 to differentiate the mononuclear cells into at least NK cells and NKT cells

Methodology Applied
Scientific EffectMonoclonal antibody binding:

Implementation Method 2

performing culturing after the first step under conditions where the mononuclear cells are preferentially differentiated into cytotoxic T cells; wherein the second step is performed in the presence of anti CD3 antibody

Methodology Applied
Scientific EffectMonoclonal antibody binding:

Data Source

PatentEP2947144B1Method for manufacturing immunocyte-containing composition, and cancer-treating composition
Publication Date: 2020.09.09 ABE
  • EP2947144B1 patent drawingFigure 1(A)~1(B-2)
  • EP2947144B1 patent drawingFigure 2(A)~2(B)
  • EP2947144B1 patent drawingFigure 3

AI summary

To provide a method in which mononuclear cells are differentiated into a good balance of NK cells, NKT cells, and T cells, and said cells are made to proliferate. The present invention provides a method for manufacturing an immune cell-containing composition, said method including the following steps: a first step in which mononuclear cells are cultured in a medium containing anti-CD16 monoclonal antibodies and either IL-2 and/or IL-15; and a second step, after the first step, in which culturing is performed under conditions that make the mononuclear cells preferentially differentiate into cytotoxic T cells. This method may also include a third step, after the second step, in which culturing is performed in a medium containing anti-CD16 monoclonal antibodies and either IL-2 and/or IL-15.