PBMC Delivery via Cell Squeeze for Immune Activation
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Solution Overview
Problem
Current methods for inducing endogenous T cell responses in immunotherapy face challenges, particularly in effectively stimulating CD8+ cytotoxic T lymphocytes and CD4+ helper T cells using disease-associated antigens, with limited efficacy of pure B cell and T cell populations and inadequate activation of antigen-presenting cells.
Innovation Solution
The use of peripheral blood mononuclear cells (PBMCs) modified with antigens and adjuvants through a process involving cell-deforming constriction and incubation, allowing efficient antigen and adjuvant delivery, enhancing antigen-presenting cell activation and immune stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If pure B cell and T cell populations are used for immunotherapy, then cell specificity is improved, but immune response efficacy deteriorates
Solution Approach 1:
The patent combines multiple cell types (B cells, T cells, and antigen-presenting cells) into a mixed PBMC population to achieve synergistic immune responses. This merging of different cell populations resolves the contradiction by maintaining cell specificity while enhancing overall immune efficacy through cooperative interactions between cell types.
Solution Approach 2:
The patent uses a universal PBMC population that encompasses multiple immune cell types rather than isolated pure populations. This multi-functional approach allows the cell preparation to perform diverse immune functions simultaneously, improving efficacy while preserving the specific functions of each cell type.
2Device complexity
If conventional antigen delivery methods are used, then process simplicity is maintained, but antigen-presenting cell activation deteriorates
Solution Approach 1:
The patent applies preliminary action by pre-conditioning PBMCs with adjuvants before antigen delivery. This pre-treatment enhances the cells' responsiveness and activation capacity, ensuring robust antigen-presenting cell activation while maintaining relative process simplicity through a sequential two-step protocol.
Solution Approach 2:
The patent introduces adjuvants as intermediary substances that mediate between the antigen and the immune system. These adjuvants enhance antigen-presenting cell activation by modulating immune responses, bridging the gap between simple antigen delivery and effective cell activation.
3Reliability
If PBMCs are conditioned with adjuvant, then antigen-presenting cell activation is improved, but process complexity increases
Solution Approach 1:
The adjuvant conditioning step is performed as a preliminary action before antigen delivery, which simplifies the overall process architecture by separating the activation enhancement step from the antigen presentation step. This sequential approach manages complexity while achieving reliable cell activation.
Solution Approach 2:
The patent maintains continuity of useful action by using the same PBMC population throughout the conditioning and antigen delivery process. The adjuvant-conditioned cells continue to function as the antigen-presenting population, eliminating the need for separate cell preparations and reducing overall process complexity.
Data Source
AI summary
The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.