Antigen-Specific Cytotoxic T-Cell Preparation Using Activated B Cells
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Solution Overview
Problem
Current cellular immunotherapy methods for treating viral and cancerous diseases are hindered by high production costs, complex processes, and long production times, particularly due to the use of dendritic cells which are time-consuming and costly.
Innovation Solution
A method utilizing B cells activated by biological response modifiers such as alpha-galactosylceramide as antigen-presenting cells to produce antigen-specific cytotoxic T cells, replacing dendritic cells and simplifying the production process by using a two-step incubation method with antigen-loaded B cells and cytokines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dendritic cells are used as antigen-presenting cells to activate T cells, then T cell activation effectiveness is improved, but production time and cost increase significantly
Solution Approach 1:
The patent uses B cells as antigen-presenting cells instead of dendritic cells. B cells are easier to obtain, cheaper to culture, and have shorter production times compared to dendritic cells, while still being capable of presenting antigens to activate T cells. This substitution resolves the contradiction by using a more efficient, less time-consuming cell type that maintains the essential function of T cell activation.
Solution Approach 2:
The patent changes the cell type parameter from dendritic cells to B cells. This parameter change fundamentally alters the production process, reducing culture time requirements and production costs while maintaining antigen presentation capability. The B cells are activated by specific stimuli and can present antigens to T cells, achieving the same functional outcome with improved efficiency.
2Reliability
If dendritic cells are used as antigen-presenting cells to activate T cells, then T cell activation effectiveness is improved, but production cost increases
Solution Approach 1:
The patent substitutes expensive dendritic cells with more economical B cells. B cells are easier to isolate from peripheral blood, require simpler culture conditions, and have lower maintenance costs. This substitution directly reduces production costs while preserving the ability to activate T cells effectively, as B cells can still process and present antigens to T cell precursors.
3Reliability
If adenoviral vectors are used to deliver antigens to monocytes, then T cell activation is effective, but production complexity and time increase
Solution Approach 1:
The patent extracts and eliminates the complex adenoviral vector system from the protocol. Instead of using viral vectors to deliver antigens to monocytes, the patent directly uses activated B cells as antigen-presenting cells. This simplification removes the need for viral vector production, purification, and handling, dramatically reducing production complexity and time while maintaining T cell activation effectiveness.
Solution Approach 2:
The patent replaces the complex, time-consuming adenoviral vector system with a simpler B cell-based system. B cells can be directly activated and used as antigen-presenting cells without requiring viral vector production. This substitution simplifies the entire production process, reducing both complexity and time requirements while achieving the same therapeutic outcome.
4Reliability
If extended culture periods are used with dendritic cells, then T cell activation effectiveness is improved, but production time increases
Solution Approach 1:
The patent uses B cells that have shorter culture requirements compared to dendritic cells. Activated B cells can be rapidly generated from peripheral blood mononuclear cells and used immediately as antigen-presenting cells. This eliminates the need for extended culture periods required by dendritic cells, significantly reducing the overall production time while maintaining effective T cell activation through rapid antigen presentation.
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 approach significantly reduces production time and cost while effectively increasing the number of antigen-specific cytotoxic T cells, enabling more efficient treatment of viral and cancerous infections.
Implementation Method 1
treating the isolated or separated B cells with any one biological response modifier selected from the group consisting of alpha-galactosylceramide, alpha-glucuronosylceramide, phosphatidylinositol tetramannoside, isoglobotrihexylceramide, ganglioside GD3, phosphatidylcholine, beta-galactosylceramide, lipophosphoglycan, glycoinositol phospholipid, alpha-galactosylceramide analogs
Implementation Method 2
delivering an antigen-encoding nucleic acid or an antigen peptide into the activated B cells
Implementation Method 3
mixing the antigen-delivered activated B cells with the mononuclear cells separated to produce a first mixture of the cells; subjecting the first mixture of the cells to a first culture/incubation
Implementation Method 4
after the first incubation, further adding a fresh batch of the antigen-delivered activated B cells to the first mixture of cells to produce a second mixture of the cells and subject the second mixture of the cells to a second incubation
Data Source
AI summary
Disclosed in the present application are: a method for preparing in vitro/ex vivo antigen-specific cytotoxic T-cells by using B cells treated with biological response modifier; and a use thereof. The cytotoxic T-cells prepared by the method of the present application can be used advantageously for treating infectious disease and cancer and the like.