Modified NKT Cells for Autoimmune Disease Treatment
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Solution Overview
Problem
There is an unmet need for effective treatments and prevention methods for autoimmune diseases, as the aberrant frequency and function of Natural Killer T (NKT) cells contribute to the pathology of these conditions, and existing therapies fail to adequately address the immune response targeting self-tissues.
Innovation Solution
Modified NKT cells with specific phenotypes, including CD3+CD56+CD8+ expressing regulatory T cell and T helper cell surface markers, are generated through culturing enriched mononuclear cell fractions with transforming growth factor beta (TGF-β) and T-cell growth factors, which are then used to treat autoimmune diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional NKT cells are used for therapy, then the immune response targeting self-tissues is not adequately controlled, but using modified NKT cells with Treg markers requires complex culture methods
Solution Approach 1:
The culture method utilizes TGF-β to induce specific phenotypic changes in NKT cells, transforming them from conventional to regulatory phenotype with enhanced immunosuppressive properties. This parameter change approach allows generation of therapeutically effective cells through controlled differentiation rather than complex isolation procedures
Solution Approach 2:
TGF-β serves as an intermediary substance that mediates the transformation of NKT cells into regulatory phenotype. This cytokine acts as a bridge between conventional NKT cells and their therapeutic regulatory form, enabling controlled phenotypic switching without requiring complex genetic or physical modifications
2Adaptability or versatility
If NKT cell-based therapy is developed, then treatment for autoimmune disease can be provided, but sufficient therapeutically competent NKT cells are not available
Solution Approach 1:
The culture method performs preliminary expansion and differentiation of NKT cells before therapeutic application. By pre-culturing enriched mononuclear cells with TGF-β and T-cell growth factors, sufficient numbers of therapeutically competent regulatory NKT cells are generated in advance, ensuring adequate cell quantity for clinical use
Solution Approach 2:
The method extracts and enriches NKT cell precursors from peripheral blood mononuclear cells, then selectively expands them in culture. This extraction approach isolates the relevant cell population from complex blood samples and multiplies them to therapeutic quantities
3Object-affected harmful factors
If autoreactive T lymphocyte proliferation is suppressed, then autoimmune disease pathology is reduced, but the mechanism to control self-tissue targeting immune response is insufficient
Solution Approach 1:
The therapy converts potentially harmful conventional NKT cells into beneficial regulatory cells through TGF-β-induced differentiation. These modified cells retain T cell functionality while acquiring immunosuppressive properties, transforming the immune response from pathogenic to protective against autoimmune pathology
Data Source
AI summary
The present invention provides modified natural killer T (NKT) cells, pharmaceutical compositions comprising the modified NKT cells and at least one pharmaceutically acceptable carrier or excipient, and uses of the modified NKT cells. Also disclosed herein are methods for enriching NKT cells and generating the modified natural killer T cells.