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Peptide-MHC-based nanovaccines for the treatment of autoimmunity: a “one size fits all” approach?

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Abstract

Nanotechnology offers enormous potential in drug delivery and in vivo imaging. Nanoparticles (NPs), for example, are being extensively tested as scaffolds to deliver anti-cancer therapeutics or imaging tags. Our recent work, discussed herein, indicates that an opportunity exists to use NPs to deliver ligands for, and trigger, cognate receptors on T lymphocytes as a way to induce therapeutic immune responses in vivo. Specifically, systemic delivery of NPs coated with Type 1 diabetes (T1D)-relevant peptide-major histocompatibility complex molecules triggered the expansion of cognate memory autoregulatory (disease-suppressing) T cells, suppressed the progression of autoimmune attack against insulin-producing beta cells, and restored glucose homeostasis. This therapeutic avenue exploits a new paradigm in the progression of chronic autoimmune responses that enables the rational design of disease-specific “nanovaccines” capable of blunting autoimmunity without impairing systemic immunity, a long sought-after goal in the therapy of these disorders. Here, we discuss the research paths that led to the discovery of this therapeutic avenue and highlight the features that make it an attractive approach for the treatment, in an antigen-specific manner, of a whole host of autoimmune diseases.

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Acknowledgments

The work described here was funded by grants from the Canadian Institutes of Health Research (CIHR), the National and Engineering Research Council of Canada (NSERC), the Juvenile Diabetes Research Foundation (JDRF), the Diabetes Association (Foothills), and the Canadian Diabetes Association. X.C.C. and S.T. are supported by studentships from the AXA Research Fund Foundation and Alberta Innovates—Health Solutions (AIHS, formerly AHFMR), respectively. P.S. is a Scientist of AIHS and a JDRF Scholar. The JMDRC is supported by the Diabetes Association (Foothills).

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  1. Julia McFarlane Diabetes Research Centre and Department of Microbiology and Infectious Diseases, Institute of Inflammation, Infection and Immunity, Faculty of Medicine, The University of Calgary, 3330 Hospital Dr. N.W., Calgary, T2N 4N1, Alberta, Canada

    Xavier Clemente-Casares, Sue Tsai, Yang Yang & Pere Santamaria

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  1. Xavier Clemente-Casares
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  2. Sue Tsai
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  4. Pere Santamaria
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Correspondence to Pere Santamaria.

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Clemente-Casares, X., Tsai, S., Yang, Y. et al. Peptide-MHC-based nanovaccines for the treatment of autoimmunity: a “one size fits all” approach?. J Mol Med 89, 733–742 (2011). https://doi.org/10.1007/s00109-011-0757-z

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