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The therapeutic potential of immunoengineering for systemic autoimmunity

Nature Reviews Rheumatology volume 20, pages 203–215 (2024)Cite this article

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Abstract

Disease-modifying drugs have transformed the treatment options for many systemic autoimmune diseases. However, an evolving understanding of disease mechanisms, which might vary between individuals, is paving the way for the development of novel agents that operate in a patient-tailored manner through immunophenotypic regulation of disease-relevant cells and the microenvironment of affected tissue domains. Immunoengineering is a field that is focused on the application of engineering principles to the modulation of the immune system, and it could enable future personalized and immunoregulatory therapies for rheumatic diseases. An important aspect of immunoengineering is the harnessing of material chemistries to design technologies that span immunologically relevant length scales, to enhance or suppress immune responses by re-balancing effector and regulatory mechanisms in innate or adaptive immunity and rescue abnormalities underlying pathogenic inflammation. These materials are endowed with physicochemical properties that enable features such as localization in immune cells and organs, sustained delivery of immunoregulatory agents, and mimicry of key functions of lymphoid tissue. Immunoengineering applications already exist for disease management, and there is potential for this new discipline to improve disease modification in rheumatology.

Key points

  • An unmet need exists for immunoregulatory disease-modifying agents for patients with rheumatological conditions who cannot tolerate immunosuppression and for partial responders and non-responders to current standards of care.

  • Immunoengineering is an emerging research area with a major focus on a systems-based approach to rescue disorders of the immune system by leveraging material chemistries to generate immunoregulators.

  • Immunoengineering advances now offer the possibility of a new class of therapeutics aimed at immunomodulation rather than at immunosuppression, which could synergize with standard-of-care therapies and personalize treatment in systemic autoimmunity.

  • Immunomodulation, tolerization and measurement of disease activity are facilitated by nanoparticles; microparticles enable sustained, localized release of immunomodulatory compounds; and macroscale materials have uses in cell therapy and as immunological niches.

  • To improve the safety, efficacy and specificity of T cell-based therapies, immunoengineering can be leveraged to enrich specific cell subsets, generate transient T cells in vivo and improve target identification.

  • Immunoengineering could aid in the diagnosis of disease, immunophenotyping for patient-stratification purposes and in developing in vitro models to study autoimmunity.

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Fig. 1: Immunoregulation and tolerization.
Fig. 2: Enabling immune cell therapy.
Fig. 3: Immunodiagnostics.
Fig. 4: In vitro models of lymphoid organs.

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  1. Department of NanoEngineering and Chemical Engineering Program, University of California, San Diego, La Jolla, CA, USA

    David A. McBride, Ryan M. Jones & Nisarg J. Shah

  2. Kao Autoimmunity Institute and Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Nunzio Bottini

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N.J.S. and N.B. are academic founders of Tekhona Inc. and have an equity interest in the company. The terms of this arrangement have been reviewed and approved by their institutions in accordance with conflict of interest policies. The remaining authors declare no competing interests.

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McBride, D.A., Jones, R.M., Bottini, N. et al. The therapeutic potential of immunoengineering for systemic autoimmunity. Nat Rev Rheumatol 20, 203–215 (2024). https://doi.org/10.1038/s41584-024-01084-x

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  • DOI: https://doi.org/10.1038/s41584-024-01084-x

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