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  • Perspective
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Bottom-up synthetic immunology

Nature Nanotechnology (2024)Cite this article

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Abstract

Infectious diseases and cancer evade immune surveillance using similar mechanisms. Targeting immune mechanisms using common strategies thus represents a promising avenue to improve prevention and treatment. Synthetic immunology can provide such strategies by applying engineering principles from synthetic biology to immunology. Synthetic biologists engineer cells by top-down genetic manipulation or bottom-up assembly from nanoscale building blocks. Recent successes in treating advanced tumours and diseases using genetically engineered immune cells highlight the power of the top-down synthetic immunology approach. However, genetic immune engineering is mostly limited to ex vivo applications and is subject to complex counter-regulation inherent to immune functions. Bottom-up synthetic biology can harness the rich nanotechnology toolbox to engineer molecular and cellular systems from scratch and equip them with desired functions. These are beginning to be tailored to perform targeted immune functions and should hence allow intervention strategies by rational design. In this Perspective we conceptualize bottom-up synthetic immunology as a new frontier field that uses nanotechnology for crucial innovations in therapy and the prevention of infectious diseases and cancer.

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Fig. 1: Schematic overview of innate and adaptive immune responses exemplified for pathogen infection.
Fig. 2: Top-down versus bottom-up synthetic immunology.
Fig. 3: Modification of immune cell interactions by bottom-up synthetic immunology.
Fig. 4: Functional selection of elite immune cells for personalized immunotherapy.

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Acknowledgements

We acknowledge the contributions of many investigators whose work could not be cited due to the length limits of this Perspective. We are grateful to K. Bajak for figure design and administrative help. K.G. acknowledges the Max Planck School Matter to Life, supported by the German Federal Ministry of Education and Research (BMBF) in collaboration with the Max Planck Society and Heidelberg University, and funding from ERC starting grant ENSYNC (grant number 101076997). K.G. and M.P. acknowledge funding from the State of Baden-Württemberg for a multi-institutional project on Synthetic Immunology within the Heidelberg Mannheim Health and Life Science Alliance (https://www.health-life-sciences.de/synthetic-immunology). All authors received funding from the Federal Ministry of Education and Research (BMBF) and the Ministry of Science Baden-Württemberg within the framework of the Excellence Strategy of the Federal and State Governments of Germany in support of the Heidelberg University Flagship Initiative Engineering Molecular Systems (FI EMS) Spotlight Project ‘Synthetic Immunology’. This publication was also supported directly by the Ministry of Science, Research and Culture Baden-Württemberg and the Helmholtz Association.

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Authors and Affiliations

  1. Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg University, Heidelberg, Germany

    Kerstin Göpfrich

  2. Biophysical Engineering Group, Max Planck Institute for Medical Research, Heidelberg, Germany

    Kerstin Göpfrich

  3. Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Michael Platten

  4. German Cancer Consortium (DKTK), Core Center Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Michael Platten

  5. Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany

    Michael Platten

  6. DKFZ Hector Cancer Institute, University Medical Center Mannheim, Mannheim, Germany

    Michael Platten

  7. Parasitology, Department of Infectious Diseases, Department of Infectious Diseases, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany

    Friedrich Frischknecht

  8. German Center for Infection Research, DZIF, Partner Site Heidelberg, Heidelberg, Germany

    Friedrich Frischknecht & Oliver T. Fackler

  9. Integrative Virology, Center of Integrative Infectious Disease Research, Department of Infectious Diseases, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany

    Oliver T. Fackler

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M.P. is an inventor on patent applications describing the identification of tumour-reactive TCRs and a founder of Tcelltech GmbH.

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Göpfrich, K., Platten, M., Frischknecht, F. et al. Bottom-up synthetic immunology. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01744-9

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