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Article ; Online: Novel delivery mechanisms for antigen-specific immunotherapy.

Neef, Tobias / Miller, Stephen D

Current opinion in endocrinology, diabetes, and obesity

2021 Volume 28, Issue 4, Page(s) 404–410

Abstract: Purpose of review: Current therapies for autoimmune disorders often employ broad suppression of the immune system. Antigen-specific immunotherapy (ASI) seeks to overcome the side-effects of immunosuppressive therapy by specifically targeting only ... ...

Abstract	Purpose of review: Current therapies for autoimmune disorders often employ broad suppression of the immune system. Antigen-specific immunotherapy (ASI) seeks to overcome the side-effects of immunosuppressive therapy by specifically targeting only disease-related autoreactive T and B cells. Although it has been in development for several decades, ASI still is not in use clinically to treat autoimmunity. Novel ways to deliver antigen may be effective in inducing ASI. Here we review recent innovations in antigen delivery. Recent findings: New ways to deliver antigen include particle and nonparticle approaches. One main focus has been the targeting of antigen-presenting cells in a tolerogenic context. This technique often results in the induction and/or expansion of regulatory T cells, which has the potential to be effective against a complex, polyclonal immune response. Summary: Whether novel delivery approaches can help bring ASI into general clinical use for therapy of autoimmune diseases remains to be seen. However, preclinical work and early results from clinical trials using these new techniques show promising signs.
MeSH term(s)	Antigens/administration & dosage ; Antigens/immunology ; Autoimmune Diseases/drug therapy ; Autoimmune Diseases/immunology ; Autoimmunity/drug effects ; Autoimmunity/immunology ; Humans ; Immune Tolerance/drug effects ; Immune Tolerance/immunology ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/immunology ; Immunotherapy/methods ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Antigens ; Immunosuppressive Agents
Language	English
Publishing date	2021-06-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000649
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Article ; Online: Rotator Cuff Tears Are Related to the Side Sleeping Position.

Richards, David P / Miller, Daniel L / MacDonald, E David / Stewart, Quinn F / Miller, Stephen D

Arthroscopy, sports medicine, and rehabilitation

2024 Volume 6, Issue 2, Page(s) 100886

Abstract: Purpose: To determine whether there was a relationship between sleep position and symptomatic partial- and full-thickness rotator cuff tears.: Methods: A consecutive series of patients that met the inclusion/exclusion criteria (n = 58) were in seen ... ...

Abstract	Purpose: To determine whether there was a relationship between sleep position and symptomatic partial- and full-thickness rotator cuff tears. Methods: A consecutive series of patients that met the inclusion/exclusion criteria (n = 58) were in seen in clinic between July 2019 and December 2019. All of these individuals had a significant partial-thickness (> 50%) or full-thickness rotator cuff tear determined by either ultrasound, magnetic resonance imaging, or both. All patients in this series either had an insidious onset of shoulder pain or their symptoms were related to the basic wear and tear of daily activities. Traumatic rotator cuff tears (those associated with a significant traumatic event such as shoulder instability, motor vehicle accidents, sports related injuries, etc.) were excluded. Previous shoulder surgery, recurrent rotator cuff tears, and worker's compensation cases also were excluded from this series. As part of the history-taking process, the patients were asked what was their preferred sleeping position-side sleeper, back sleeper, or stomach sleeper. A χ Results: Of the 58 subjects, 52 of the patients were side sleepers, 4 were stomach sleepers, 1 was a back sleeper, and 1 preferred all 3 positions. Statistical analysis, using the χ Conclusions: In our study, there appeared to be a relationship between the preference of being a side sleeper and the presence of a rotator cuff tear. Level of evidence: Level IV, prognostic case series.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ISSN	2666-061X
ISSN (online)	2666-061X
DOI	10.1016/j.asmr.2024.100886
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Potential for Targeting Myeloid Cells in Controlling CNS Inflammation.

Ifergan, Igal / Miller, Stephen D

Frontiers in immunology

2020 Volume 11, Page(s) 571897

Abstract: Multiple Sclerosis (MS) is characterized by immune cell infiltration to the central nervous system (CNS) as well as loss of myelin. Characterization of the cells in lesions of MS patients revealed an important accumulation of myeloid cells such as ... ...

Abstract	Multiple Sclerosis (MS) is characterized by immune cell infiltration to the central nervous system (CNS) as well as loss of myelin. Characterization of the cells in lesions of MS patients revealed an important accumulation of myeloid cells such as macrophages and dendritic cells (DCs). Data from the experimental autoimmune encephalomyelitis (EAE) model of MS supports the importance of peripheral myeloid cells in the disease pathology. However, the majority of MS therapies focus on lymphocytes. As we will discuss in this review, multiple strategies are now in place to target myeloid cells in clinical trials. These strategies have emerged from data in both human and mouse studies. We discuss strategies targeting myeloid cell migration, growth factors and cytokines, biological functions (with a focus on miRNAs), and immunological activities (with a focus on nanoparticles).
MeSH term(s)	Animals ; Cell Movement ; Central Nervous System/physiology ; Cytokines/metabolism ; Encephalomyelitis, Autoimmune, Experimental/therapy ; Humans ; Mice ; MicroRNAs/genetics ; Multiple Sclerosis/therapy ; Myeloid Cells/physiology ; Nanoparticles ; Neurogenic Inflammation/therapy
Chemical Substances	Cytokines ; MicroRNAs
Keywords	covid19
Language	English
Publishing date	2020-10-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.571897
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Use of Biodegradable Nanoparticles for Tolerogenic Therapy of Allergic Inflammation.

Smarr, Charles B / Miller, Stephen D

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1799, Page(s) 353–358

Abstract: Antigen-specific tolerance is the ultimate aim of treatment of allergic diseases. Here, we describe methods for the use of biodegradable nanoparticles to safely induce tolerance for the prevention and treatment of allergic inflammation in mice. Antigen ... ...

Abstract	Antigen-specific tolerance is the ultimate aim of treatment of allergic diseases. Here, we describe methods for the use of biodegradable nanoparticles to safely induce tolerance for the prevention and treatment of allergic inflammation in mice. Antigen is either conjugated to the surface of carboxylated poly(lactide-co-glycolide) (PLG) or encapsulated within PLG nanoparticles, and the resulting antigen-associated nanoparticles are then washed prior to intravenous injection to inhibit antigen-specific allergic immune responses.
MeSH term(s)	Animals ; Antigens/administration & dosage ; Antigens/chemistry ; Antigens/immunology ; Desensitization, Immunologic ; Hypersensitivity/immunology ; Hypersensitivity/therapy ; Immune Tolerance ; Mice ; Nanoparticles/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Silver/chemistry ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Theranostic Nanomedicine
Chemical Substances	Antigens ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Silver (3M4G523W1G)
Language	English
Publishing date	2018-06-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7896-0_25
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Article ; Online: Tolerogenic Nanoparticles to Treat Islet Autoimmunity.

Neef, Tobias / Miller, Stephen D

Current diabetes reports

2017 Volume 17, Issue 10, Page(s) 84

Abstract: Purpose of review: The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is ... ...

Abstract	Purpose of review: The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is preferable. The application of nanomedicine to the problem of T1D can take different forms, but one promising way is the development of tolerogenic nanoparticles, the aim of which is to mitigate the islet-destroying autoimmunity. We review the topic and highlight recent strategies to produce tolerogenic nanoparticles for the purpose of treating T1D. Recent findings: Several groups are making progress in applying tolerogenic nanoparticles to rodent models of T1D, while others are using nanotechnology to aid other potential T1D treatments such as islet transplant and islet encapsulation. The strategies behind how nanoparticles achieve tolerance are varied. It is likely the future will see even greater diversity in tolerance induction strategies as well as a greater focus on how to translate this technology from preclinical use in mice to treatment of T1D in humans.
MeSH term(s)	Animals ; Autoimmunity ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/therapy ; Humans ; Immune Tolerance ; Islets of Langerhans/immunology ; Nanoparticles/therapeutic use
Language	English
Publishing date	2017-08-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2065167-3
ISSN	1539-0829 ; 1534-4827
ISSN (online)	1539-0829
ISSN	1534-4827
DOI	10.1007/s11892-017-0914-z
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Article ; Online: Potential targeting of B7-H4 for the treatment of cancer.

Podojil, Joseph R / Miller, Stephen D

Immunological reviews

2017 Volume 276, Issue 1, Page(s) 40–51

Abstract: Observations noting the presence of white blood cell infiltrates within tumors date back more than a century, however the cellular and molecular mechanisms regulating tumor immunity continue to be elucidated. The recent successful use of monoclonal ... ...

Abstract	Observations noting the presence of white blood cell infiltrates within tumors date back more than a century, however the cellular and molecular mechanisms regulating tumor immunity continue to be elucidated. The recent successful use of monoclonal antibodies to block immune regulatory pathways to enhance tumor-specific immune responses for the treatment of cancer has encouraged the identification of additional immune regulatory receptor/ligand pathways. Over the past several years, a growing body of data has identified B7-H4 (VTCN1/B7x/B7S1) as a potential therapeutic target for the treatment of cancer. The potential clinical significance of B7-H4 is supported by the high levels of B7-H4 expression found in numerous tumor tissues and correlation of the level of expression on tumor cells with adverse clinical and pathologic features, including tumor aggressiveness. The biological activity of B7-H4 has been associated with decreased inflammatory CD4
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/metabolism ; Forkhead Transcription Factors/metabolism ; Humans ; Immunotherapy/methods ; Macrophages/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; T-Lymphocytes, Regulatory/immunology ; Tumor Escape ; Tumor Microenvironment ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/immunology ; V-Set Domain-Containing T-Cell Activation Inhibitor 1/metabolism
Chemical Substances	Antibodies, Monoclonal ; Antigens, Neoplasm ; FOXP3 protein, human ; Forkhead Transcription Factors ; V-Set Domain-Containing T-Cell Activation Inhibitor 1 ; VTCN1 protein, human
Language	English
Publishing date	2017-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12530
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Article ; Online: Engineering nanoparticle therapeutics for food allergy.

Rad, Laila M / Arellano, Gabriel / Podojil, Joseph R / O'Konek, Jessica J / Shea, Lonnie D / Miller, Stephen D

The Journal of allergy and clinical immunology

2023 Volume 153, Issue 3, Page(s) 549–559

Abstract: Food allergy is a growing public health issue among children and adults that can lead to life-threatening anaphylaxis following allergen exposure. The criterion standard for disease management includes food avoidance and emergency epinephrine ... ...

Abstract	Food allergy is a growing public health issue among children and adults that can lead to life-threatening anaphylaxis following allergen exposure. The criterion standard for disease management includes food avoidance and emergency epinephrine administration because current allergen-specific immunotherapy treatments are limited by adverse events and unsustained desensitization. A promising approach to remedy these shortcomings is the use of nanoparticle-based therapies that disrupt disease-driving immune mechanisms and induce more sustained tolerogenic immune pathways. The pathophysiology of food allergy includes multifaceted interactions between effector immune cells, including lymphocytes, antigen-presenting cells, mast cells, and basophils, mainly characterized by a T
MeSH term(s)	Child ; Adult ; Humans ; Food Hypersensitivity ; Desensitization, Immunologic ; Food ; Allergens ; Nanoparticles
Chemical Substances	Allergens
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.10.013
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Article ; Online: The immune system and metabolic products in epilepsy and glioma-associated epilepsy: emerging therapeutic directions.

Tripathi, Shashwat / Nathan, Cody L / Tate, Matthew C / Horbinski, Craig M / Templer, Jessica W / Rosenow, Joshua M / Sita, Timothy L / James, Charles D / Deneen, Benjamin / Miller, Stephen D / Heimberger, Amy B

JCI insight

2024 Volume 9, Issue 1

Abstract: Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently ... ...

Abstract	Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. Metabolic modulation of the IDH1-mutant pathway provides a dual pathway for reversing immune suppression and dampening seizure activity. Elucidating the relationship between neurons and immunoreactivity is an area for the prioritization and development of the next era of ASMs.
MeSH term(s)	Animals ; Humans ; Quality of Life ; Epilepsy/drug therapy ; Epilepsy/etiology ; Glioma/complications ; Glioma/drug therapy ; Drug Resistant Epilepsy ; Immune System ; Tumor Microenvironment
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.174753
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Article: Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.

Lyman, Kyle A / Han, Ye / Robinson, Andrew P / Weinberg, Samuel E / Fisher, Daniel W / Heuermann, Robert J / Lyman, Reagan E / Kim, Dong Kyu / Ludwig, Andreas / Chandel, Navdeep S / Does, Mark D / Miller, Stephen D / Chetkovich, Dane M

Frontiers in cellular neuroscience

2024 Volume 18, Page(s) 1321682

Abstract: Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. ... ...

Abstract	Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I
Language	English
Publishing date	2024-02-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2024.1321682
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Article ; Online: Mechanistic contributions of Kupffer cells and liver sinusoidal endothelial cells in nanoparticle-induced antigen-specific immune tolerance

Casey, Liam M. / Hughes, Kevin R. / Saunders, Michael N. / Miller, Stephen D. / Pearson, Ryan M. / Shea, Lonnie D.

Biomaterials. 2022 Apr., v. 283 p.121457-

2022

Abstract: The intravenous delivery of disease-relevant antigens (Ag) by polymeric nanoparticles (NP-Ags) has demonstrated Ag-specific immune tolerance in autoimmune and allergic disorders as well as allogeneic transplant rejection. NP-Ags are observed to ... ...

Abstract	The intravenous delivery of disease-relevant antigens (Ag) by polymeric nanoparticles (NP-Ags) has demonstrated Ag-specific immune tolerance in autoimmune and allergic disorders as well as allogeneic transplant rejection. NP-Ags are observed to distribute to the spleen, which has an established role in the induction of immune tolerance. However, studies have shown that the spleen is dispensable for NP-Ag-induced tolerance, suggesting significant contributions from other immunological sites. Here, we investigated the tolerogenic contributions of Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) to NP-Ag-induced tolerance in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Intravenously delivered Ag-conjugated poly(lactide-co-glycolide) NPs (PLG-Ag) distributed largely to the liver, where they associated with both KCs and LSECs. This distribution was accompanied by CD4 T cell accumulation, clonal deletion, and PD-L1 expression by KCs and LSECs. Ex vivo co-cultures of PLG-Ag-treated KCs or LSECs with Ag-specific CD4 T cells resulted in PGE₂ and IL-10 or PGE₂ secretion, respectively. KC depletion and adoptive transfer experiments demonstrated that KCs were sufficient, but not necessary, to mediate PLG-Ag-induced tolerance in EAE. The durability of PLG-Ag-induced tolerance in the absence of KCs may be attributed to the distribution of PLG-Ags to LSECs, which demonstrated similar levels of PD-L1, PGE₂, and T cell stimulatory ability. Collectively, these studies provide mechanistic support for the role of liver KCs and LSECs in Ag-specific tolerance for a biomaterial platform that is currently being evaluated in clinical trials.
Keywords	CD4-positive T-lymphocytes ; biocompatible materials ; coculture ; durability ; encephalitis ; graft rejection ; immunosuppression ; interleukin-10 ; intravenous injection ; liver ; mice ; polymers ; sclerosis ; secretion ; spleen ; PLG ; Nanoparticles ; Immune tolerance ; Immunomodulation ; Kupffer cells ; Liver sinusoidal endothelial cells
Language	English
Dates of publication	2022-04
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121457
Database	NAL-Catalogue (AGRICOLA)

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