Extremely short bioavailability and fast pharmacodynamic effects of pMHC-based nanomedicines

Yang, Yang; Ellestad, Kristofor K.; Singha, Santiswarup; Uddin, Muhammad Myn; Clarke, Robert; Mondal, Debajyoti; Garabatos, Nahir; Solé, Patricia; Fandos, César; Serra, Pau; Santamaría, Pere

doi:10.1016/j.jconrel.2021.08.043

Cited by 7 publications

(8 citation statements)

References 28 publications

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“…Unfortunately, this cannot be tested in vitro, as these compounds (as is also the case for the pMHCII-NP compounds that trigger cognate TR1 cell formation) can only re-program CD4+ and LiNKT cells in vivo. The reasons behind this remain unclear, but one possibility is that sustained in vitro culture of responder T cells with cognate MHC-NPs somehow overrides in vivo re-programming effects that might be driven by relatively short, but repetitive exposures of cognate T cells to these compounds in vivo, based on their extremely fast pharmacokinetic behavior 43 .…”

Section: Discussionmentioning

confidence: 99%

Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity

et al. 2022

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Invariant NKT (iNKT) cells comprise a heterogeneous group of non-circulating, tissue-resident T lymphocytes that recognize glycolipids, including alpha-galactosylceramide (αGalCer), in the context of CD1d, but whether peripheral iNKT cell subsets are terminally differentiated remains unclear. Here we show that mouse and human liver-resident αGalCer/CD1d-binding iNKTs largely correspond to a novel Zbtb16+Tbx21+Gata3+MaflowRorc– subset that exhibits profound transcriptional, phenotypic and functional plasticity. Repetitive in vivo encounters of these liver iNKT (LiNKT) cells with intravenously delivered αGalCer/CD1d-coated nanoparticles (NP) trigger their differentiation into immunoregulatory, IL-10+IL-21-producing Zbtb16highMafhighTbx21+Gata3+Rorc– cells, termed LiNKTR1, expressing a T regulatory type 1 (TR1)-like transcriptional signature. This response is LiNKT-specific, since neither lung nor splenic tissue-resident iNKT cells from αGalCer/CD1d-NP-treated mice produce IL-10 or IL-21. Additionally, these LiNKTR1 cells suppress autoantigen presentation, and recognize CD1d expressed on conventional B cells to induce IL-10+IL-35-producing regulatory B (Breg) cells, leading to the suppression of liver and pancreas autoimmunity. Our results thus suggest that LiNKT cells are plastic for further functional diversification, with such plasticity potentially targetable for suppressing tissue-specific inflammatory phenomena.

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Section: Discussionmentioning

confidence: 99%

Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity

et al. 2022

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“…It is a component of more than 25 selenium proteases and enzyme-catalyzed sites in vivo and plays a vital part in protecting tissues and cells from oxidative damage, but Se deficiency has been linked to a variety of diseases, including liver damage. 120 Selenium nanoparticles (Se NPs) have aroused increasing concerns because of their excellent properties and biological activity. Se NPs are considered a potential selenium supplement because they show great potential in nutritional supplements, chemoprevention, chemotherapeutic, and nanomedicine delivery applications.…”

Section: Reviewmentioning

confidence: 99%

“…NPs coated with pMHC molecules related to autoimmune diseases could effectively solve the inflammation in a variety of organ-specific autoimmune disease models and have a certain effect on AIH without damaging normal immunity. 120,122,123 Santamaria et al and Khadra et al both carried out relevant studies on pMHC NPs. Santamaria et al mainly studied the properties of pMHC NPs.…”

Section: Reviewmentioning

confidence: 99%

Section: Nano-drug Delivery Platform For Autoimmune Hepatitismentioning

confidence: 99%

Section: Nano-drug Delivery Platform For Autoimmune Hepatitismentioning

confidence: 99%

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Recent advances on drug delivery nanoplatforms for the treatment of autoimmune inflammatory diseases

et al. 2022

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Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

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Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease‐causing cells. New immunotherapies that induce potent and selective antigen‐specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting—or even reversing—disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen‐specific tolerance and provide commentary on the current state of the clinical development of these technologies.

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Extremely short bioavailability and fast pharmacodynamic effects of pMHC-based nanomedicines

Cited by 7 publications

References 28 publications

Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity

Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity

Recent advances on drug delivery nanoplatforms for the treatment of autoimmune inflammatory diseases

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

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