Modified Immunocyte with Exogenous TCR Chains for NK-T Cell Activation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immunotherapy methods for enhancing innate immunity face challenges in effectively proliferating and activating natural killer T cells, which are essential for inducing a robust immune response, often resulting in inadequate cell proliferation and activation.
Innovation Solution
The development of modified immunocytes expressing an exogenous invariant T-cell receptor α chain and β chain, which form a dimer on the cell surface, specifically using human Vα24 and Vβ11 or mouse Vα14 and Vβ8.2/Vβ7/Vβ2 chains, to enhance Th1 cytokine production and cell proliferation upon CD1d ligand stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods are used to culture and proliferate natural killer T cells, then the cells can be expanded in number, but the cells fail to proliferate and activate as desired depending on the state of the lymphocytes collected
Solution Approach 1:
The invention introduces exogenous invariant T-cell receptor chains (Vα24 and Vβ11 for human, Vα14 and Vβ8.2/Vβ7/Vβ2 for mouse) to modify the immunocyte's receptor parameters. This parameter change enables consistent recognition of CD1d ligands regardless of the original lymphocyte state, resolving the reliability issue while maintaining productivity.
Solution Approach 2:
The exogenous T-cell receptor chains act as intermediaries that bridge the immunocyte to the CD1d ligand. This intermediary mechanism ensures reliable activation through a standardized recognition pathway, overcoming the variability in natural lymphocyte states.
2Quantity of substance
If the proportion of natural killer T cells in lymphocytes is low, then the innate immunity response is limited, but increasing the cell number through culture requires complex amplification processes
Solution Approach 1:
The modified immunocytes are designed to self-activate upon encountering CD1d ligands in the body. The exogenous T-cell receptor chains enable the cells to autonomously recognize and respond to their target, eliminating the need for complex external culture and amplification processes.
3Adaptability or versatility
If natural killer T cells are used for immunotherapy, then antigen-specific immunity is enhanced, but the therapy does not cover cases requiring innate immunity activation
Solution Approach 1:
The modified immunocytes possess dual functionality: they maintain antigen-specific recognition capabilities while simultaneously gaining the ability to recognize CD1d ligands and activate innate immunity. This multi-functionality allows the same cell type to address both antigen-specific and innate immunity requirements.
Data Source
Figure 1A~1C
Figure 2A~2D
Figure 3A~3B
AI summary
A modified immunocyte: (1) which expresses an exogenous unmodified T cell receptor α-chain and an exogenous T cell receptor β-chain on the cell surface thereof; or (2) which contains a polynucleotide encoding a T cell receptor α-chain and a polynucleotide encoding a T cell receptor β-chain. Thus, a new tool whereby immunity can be appropriately induced in vivo is provided.