Enhanced NK Cell Population for Solid Tumor Infiltration
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Solution Overview
Problem
Current NK cell therapies for treating tumors, including those using CAR-T cells and NK cells, face challenges such as high development costs, regulatory complexities, and insufficient antitumor activity due to weak chemotaxis and infiltration issues, particularly for solid tumors.
Innovation Solution
A cell population comprising CCR5-positive, CCR6-positive, CXCR3-positive, and CD3-negative cells with enhanced expression of CD11a, CD11c, integrin α1, and integrin α3, and reduced expression of CD3 and other markers, which are cultured to increase their chemotactic and cytotoxic capabilities for tumor infiltration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If NK cells are cultured ex vivo to increase their number for therapy, then the quantity of NK cells is improved, but their chemotaxis and infiltration capability deteriorates
Solution Approach 1:
The patent applies parameter changes by modifying the culture conditions (adding specific cytokines like IL-2, IL-15, IL-12, and other growth factors) to simultaneously increase NK cell quantity while maintaining or enhancing their chemotaxis capability. The culture medium composition and cytokine concentrations are optimized to preserve functional properties during expansion.
Solution Approach 2:
The patent uses preliminary action by pre-treating NK cells with specific cytokines and growth factors during the culture period before transplantation. This preliminary conditioning enhances the cells' chemotaxis and cytotoxicity capabilities in advance, ensuring they maintain high functionality after expansion and upon reaching the tumor site.
2Manufacturing precision
If CAR-T cells are genetically modified to acquire antigen specificity, then the specificity to target tumor is improved, but the migration to solid tumor deteriorates
Solution Approach 1:
The patent creates a composite cell product by combining NK cells (which naturally lack antigen specificity but have strong cytotoxicity) with genetic modifications that introduce tumor-specific receptors. This composite approach merges the advantages of both cell types: the cytotoxic power of NK cells with the target specificity of CAR-T cells, while avoiding the migration issues of genetically modified T cells.
Solution Approach 2:
The patent uses copying by introducing chimeric antigen receptor genes into NK cells, allowing them to acquire tumor-specific recognition capabilities without undergoing the extensive genetic modification required for CAR-T cells. This copying of antigen recognition functionality enables NK cells to target tumors effectively while maintaining their natural migration properties.
3Quantity of substance
If NK cells are cultured with high proliferation to achieve sufficient dose, then the quantity of NK cells is improved, but the therapeutic effect deteriorates
Solution Approach 1:
The patent applies parameter changes by optimizing culture conditions including cytokine concentrations (IL-2, IL-15, IL-12), culture duration, cell density, and medium composition to achieve high NK cell proliferation while preserving their cytotoxic function, chemotaxis capability, and overall therapeutic effectiveness.
Solution Approach 2:
The patent uses preliminary action by conditioning NK cells with specific cytokine combinations and culture protocols before transplantation. This preliminary enhancement ensures that even after extensive proliferation, the cells arrive at the tumor site with high cytotoxic activity and functional readiness, maintaining reliable therapeutic effect despite large expansion numbers.
Data Source
AI summary
The present invention relates to an immunocyte having higher cytotoxic activity, and a pharmaceutical composition for NK cell therapies, for which high effect can be expected. The present invention provides a cell population including CCR5-positive, CCR6-positive, CXCR3-positive, and CD3-negative cells. The present invention provides the cell population, wherein the CCR5-positive, CCR6-positive, CXCR3-positive, and CD3-negative cells further highly express CD11c. The present invention provides a CCR5-positive, CCR6-positive, CXCR3-positive, and CD3-negative cell, which infiltrates into a solid tumor. The present invention also provides a pharmaceutical composition containing such a cell population and a pharmaceutically acceptable additive. The present invention further provides a method for producing the aforementioned cell population.