PD-L1– and calcitriol-dependent liposomal antigen-specific regulation of systemic inflammatory autoimmune disease

Galea, Ryan; Nel, Hendrik J.; Talekar, Meghna; Liu, Xiao; Ooi, Joshua D.; Huynh, Megan; Hadjigol, Sara; Robson, Kate; Ting, Yi Tian; Cole, Suzanne; Cochlin, Karyn; Hitchcock, Shannon; Zeng, Bijun; Yekollu, Suman; Boks, Martine A.; Goh, Natalie; Roberts, Helen; Rossjohn, Jamie; Reid, Hugh Harrington; Boyd, Ben J.; Malaviya, Ravi; Shealy, David J.; Baker, Daniel; Madakamutil, Loui; Kitching, A. Richard; O’Sullivan, B.; Thomas, Ranjeny

doi:10.1172/jci.insight.126025

Cited by 54 publications

(49 citation statements)

References 68 publications

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“…Most importantly, VD3-raised DCs show tolerogenic stability in face of repeated rechallenge with pro-inflammatory stimuli, making VD3 a robust DC-tolerizing candidate in an already inflamed environment ( 163 ). In line with that, several recent studies in mice demonstrated that nanoparticles loaded with VD3 and OVA induced tolerogenic DCs with in vitro and in vivo suppressive capacity of OVA-specific T cells ( 164 , 165 ). Additionally, subcutaneous injection of VD3-loaded particles resulted in effective targeting of PD-L1 high draining lymph node DCs, resulting in amelioration of a RA disease model ( 165 ).…”

Section: Fostering Immune Tolerance With Dc-targeted Liposome Vaccinessupporting

confidence: 65%

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

Nagy

Haas²,

Geijtenbeek³

et al. 2021

Front. Immunol.

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Dendritic cells (DCs) are paramount in initiating and guiding immunity towards a state of activation or tolerance. This bidirectional capacity of DCs sets them at the center stage for treatment of cancer and autoimmune or allergic conditions. Accordingly, many clinical studies use ex vivo DC vaccination as a strategy to boost anti-tumor immunity or to suppress immunity by including vitamin D3, NF-κB inhibitors or retinoic acid to create tolerogenic DCs. As harvesting DCs from patients and differentiating these cells in vitro is a costly and cumbersome process, in vivo targeting of DCs has huge potential as nanoparticulate platforms equipped with activating or tolerogenic adjuvants can modulate DCs in their natural environment. There is a rapid expansion of the choices of nanoparticles and activation- or tolerance-promoting adjuvants for a therapeutic vaccine platform. In this review we highlight the most recent nanomedical approaches aimed at inducing immune activation or tolerance via targeting DCs, together with novel fundamental insights into the mechanisms inherent to fostering anti-tumor or tolerogenic immunity.

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Section: Fostering Immune Tolerance With Dc-targeted Liposome Vaccinessupporting

confidence: 65%

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

Nagy

Haas²,

Geijtenbeek³

et al. 2021

Front. Immunol.

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“…Liposomes were prepared by the thin film hydration method (19). Briefly, L-a-phosphatidylcholine (egg) (Avanti Polar Lipids, Alabaster, AL) and L-a-phosphatidylglycerol (egg) (Avanti Polar Lipids) were dissolved in a 9:1 ratio in chloroform/ethanol and evaporated to prepare a thin film under reduced pressure in a rotary evaporator.…”

Section: Liposome Formulation and Treatmentmentioning

confidence: 99%

“…Dendritic cells (DC) in both NOD mice and humans with T1D were shown to have constitutive NF-kB activation and an activated phenotype (16,17), which may pose a barrier to tolerance induction. Previously, we showed that liposomes could be used to deliver an NF-kB inhibitor and Ag to APCs, resulting in Treg induction and suppression of inflammatory arthritis (18,19). In this current study, we coencapsulated BDC2.5 mim with the NF-kB inhibitor, 1a,25-dihydroxyvitamin D3 (calcitriol), in liposomes then used I-A g7 /BDC2.5 mim tetramers to elucidate their impact on endogenous ChgA-specific CD4 + T cells in the physiological setting of the NOD mouse model of disease.…”

mentioning

confidence: 99%

Regulatory T Cells Induced by Single-Peptide Liposome Immunotherapy Suppress Islet-Specific T Cell Responses to Multiple Antigens and Protect from Autoimmune Diabetes

Bergot

Buckle

Cikaluru

et al. 2020

The Journal of Immunology

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Ag-specific tolerizing immunotherapy is considered the optimal strategy to control type 1 diabetes, a childhood disease involving autoimmunity toward multiple islet antigenic peptides. To understand whether tolerizing immunotherapy with a single peptide could control diabetes driven by multiple Ags, we coencapsulated the high-affinity CD4 + mimotope (BDC2.5 mim ) of islet autoantigen chromogranin A (ChgA) with or without calcitriol (1a,25-dihydroxyvitamin D3) into liposomes. After liposome administration, we followed the endogenous ChgA-specific immune response with specific tetramers. Liposome administration s.c., but not i.v., induced ChgA-specific Foxp3 + and Foxp3 2 PD1 + CD73 + ICOS + IL-10 + peripheral regulatory T cells in prediabetic mice, and liposome administration at the onset of hyperglycemia significantly delayed diabetes progression. After BDC2.5 mim /calcitriol liposome administration, adoptive transfer of CD4 + T cells suppressed the development of diabetes in NOD severe combined immunodeficiency mice receiving diabetogenic splenocytes. After BDC2.5 mim /calcitriol liposome treatment and expansion of ChgA-specific peripheral regulatory T cells. IFN-g production and expansion of islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8 + T cells were also suppressed in pancreatic draining lymph node, demonstrating bystander tolerance at the site of Ag presentation. Thus, liposomes encapsulating the single CD4 + peptide, BDC2.5 mim , and calcitriol induce ChgA-specific CD4 + T cells that regulate CD4 + and CD8 + self-antigen specificities and autoimmune diabetes in NOD mice.

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“…These include small-to mid-sized firms focused on research and development (R&D), as well as multinational companies like Pfizer, Eli Lilly and Company, Novartis, and Sanofi, to name a few. Moreover, a promising shift within the nanomedicine research community is the additional focus on cardiovascular [29], autoimmune [30,31], neurological [32], infectious [33], and genetic and rare diseases [34]. RNA-based synthetic vaccines are another emerging area with high potential for nanomedicine [35][36][37].…”

mentioning

confidence: 99%