Artificial immune system: methods of use
Inventors
Warren, William L • Fahlenkamp, Heather • Higbee, Russell • Kachurin, Anatoly • Li, Conan • Nguyen, Mike • Parkhill, Robert • Sanchez-Schmitz, Guzman • Irvine, Darrell J. • Randolph, Gwendalyn J. • Hacohen, Nir • Torbett, Bruce
Assignees
Scripps Research Institute • Massachusetts Institute of Technology • Icahn School of Medicine at Mount Sinai • Sanofi Pasteur VaxDesign Corp • Whitehead Institute for Biomedical Research
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Abstract
The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interaction with the immune system.
Core Innovation
The patent describes an integrated artificial immune system (AIS) platform that includes multiple engineered immunologic tissue constructs combined to model immune responses in vitro. The AIS comprises a vaccination site configured as a skin and/or mucosal equivalent with vascular and lymphatic endothelium, a lymphoid tissue equivalent (LTE) configured to mimic lymph node geometry and T and B organization, and linked lymphatic and blood vascular pathways for communication between the constructs.
The vaccination site construct and the lymphoid tissue equivalent are integrated such that immune-cell trafficking and immune-cell interactions are modeled across compartments. The platform is configured for in vitro analysis of immune-cell trafficking, dendritic cell maturation, T and B cell activation, and antibody production, using the linked lymphatic/blood vascular network equivalents to reproduce aspects of immune-system processes.
The platform is positioned for modular and miniaturized implementation in an immunobioreactor configured to support controlled in vitro modeling. The disclosed configurations include chemokine controlled release, directed cell migration using chemotaxis and magnetic microbeads, microcarrier-based LTE zoning, and optional optically diagnosable and magnet-assisted configurations, together with example-driven readouts such as antibody titers and immune activity measurements.
Claims Coverage
Not explicitly described in patent (no claims were provided).
Not explicitly described in patent (no independent claims were provided).
Stated Advantages
Enables rapid vaccine efficacy testing and analysis of immune-cell trafficking.
Allows in vitro modeling of immune-cell trafficking, dendritic cell maturation, T/B cell activation, and antibody production.
Supports modular and miniaturized immunobioreactor-based configurations for in vitro immune-system ensemble modeling.
Provides options for controlled chemokine delivery, directed cell migration, and optically diagnosable or magnet-assisted configurations for immune response analysis.
Documented Applications
Rapid vaccine efficacy testing and analysis of immune-cell trafficking.
In vitro modeling and analysis of dendritic cell maturation, T/B cell activation, and antibody production.
Modeling immune responses in an integrated artificial immune system platform using linked vaccination site, lymphoid tissue equivalent, and vascular/lymphatic pathways.
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