In-Vitro Lymphoid Cell Clusters for Human Immune Response Modeling
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Solution Overview
Problem
Current methods for studying adaptive immunity, such as inbred mouse studies, lack a system that replicates key features like affinity maturation and class switching, making it difficult to understand human vaccine responses effectively.
Innovation Solution
An in-vitro cell cluster comprising lymphoid cells with a germinal center and T-cells is developed, capable of maintaining a functional organization for at least 24 hours, which can be modulated by adjuvants and exposed to antigens to simulate immune responses, including antibody production and affinity maturation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If inbred mouse studies are used to study adaptive immunity, then a wealth of information about immune mechanisms can be obtained, but the system fails to replicate key features like affinity maturation and class switching, making it difficult to predict human vaccine responses
Solution Approach 1:
The patent creates an in vitro organotypic system that copies the essential structural and functional features of human lymphoid organs, including germinal centers with follicular dendritic cells, B cells, and T cells. This human-based model system replicates key immune processes like affinity maturation and class switching that were missing in mouse models, thereby improving predictive value for human vaccine responses while maintaining the versatility to study multiple aspects of adaptive immunity
2Adaptability or versatility
If complex in vivo mouse models are used to study adaptive immunity, then comprehensive immune responses can be observed, but the methods are difficult or impossible to confirm in humans and show poor predictive value
Solution Approach 1:
The patent transitions from in vivo mouse models to an in vitro human-based organotypic system, changing the fundamental parameters of the model system. By using human lymphoid cells and maintaining human-specific immune processes like affinity maturation and class switching in culture, the system achieves both comprehensive observation capabilities and high predictive value for human responses
3Loss of information
If traditional in vivo studies are used, then important information about immune mechanisms can be obtained, but many mechanistic aspects remain inaccessible due to lack of systems that replicate affinity maturation and class switching
Solution Approach 1:
The in vitro organotypic system is designed to self-organize and replicate human lymphoid architecture spontaneously when human lymphoid cells are cultured under appropriate conditions. The system autonomously develops germinal centers, follicular dendritic cell networks, and functional zones without requiring complex external manipulation, thereby making mechanistic information accessible while maintaining the ability to replicate affinity maturation and class switching
Data Source
AI summary
Disclosed herein are methods, systems and devices to model adaptive immune responses and develop and/or test improved antibodies, vaccines, and other therapeutic agents. The adaptive immune responses can be modeled using lymphoid tissue derived from a subject.