NK Cell Donor Selection Using CISH Genotype for High Proliferation

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Solution Overview

Problem

Conventional methods for proliferating NK cells are expensive and result in low amplification rates, often leading to unsuitable NK cell-based immune cell therapies due to the proliferation of other lymphocytes like T cells, necessitating a method to select NK cells with high proliferation rates and cancer cell killing ability.

Innovation Solution

Select donor sources based on the CISH gene's rs414171 single nucleotide polymorphism genotype, specifically identifying and selecting donors with AT or TT genotypes, and co-culturing NK cells with genetically engineered feeder cells expressing membrane-bound IL-18 and IL-21.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional methods using high concentrations of cytokines are used to proliferate NK cells, then NK cell amplification is achieved, but the cost is high and the amplification rate is low

Engineering Contradiction:

ImproveNK cell amplificationVSAvoidcost

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The invention changes the parameter of donor selection by identifying specific SNP genotypes (rs414171: AT or TT) in the CISH gene, which naturally predispose NK cells to higher proliferation rates. This genetic parameter change eliminates the need for high concentrations of expensive cytokines, thereby reducing cost while maintaining or improving amplification efficiency

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If conventional methods are used to proliferate NK cells, then some amplification is achieved, but the proliferation of other lymphocytes like T cells occurs making the therapy unsuitable

Engineering Contradiction:

ImproveNK cell amplificationVSAvoidNK cell purity

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The invention performs preliminary action by selecting donors with specific CISH gene genotypes (rs414171: AT or TT) before NK cell proliferation. This pre-selection ensures that the NK cells derived from these donors inherently exhibit high proliferation rates and specificity, preventing the unwanted proliferation of other lymphocyte types and ensuring therapeutic suitability

Inventive Principle:

Principle #10Preliminary action

3Productivity

If various culture conditions are optimized to improve NK cell proliferation rate, then amplification is enhanced, but the process complexity increases

Engineering Contradiction:

ImproveNK cell proliferation rateVSAvoidculture condition optimization

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The invention changes the fundamental parameter from culture condition optimization to genetic parameter selection. By selecting donors with specific SNP genotypes (rs414171: AT or TT) in the CISH gene, the method achieves high NK cell proliferation rates through inherent genetic characteristics rather than through complex optimization of cytokine compositions, nutrient cells, medium formulations, and cell ratios

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4671382A1Method for selecting NK cell donor source

Publication Date: 2025.12.31 ENCELL CO LTD

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AI summary

The present invention relates to a method of selecting a donor source for NK cells with enhanced proliferative capacity, wherein specific single nucleotide polymorphisms (SNPs) of the CISH gene are identified. According to the present invention, in the context of cell therapy comprising NK cells, the method addresses the issue of varying efficacy of NK cells depending on the donor source, thereby enabling the production of NK cells with superior proliferative capacity and consistent quality.