The effect of an <i>ex vivo</i> boosted immune cell therapy on canine atopic dermatitis: an open, uncontrolled pilot study

Bae, Seulgi; Kim, Kijung; Oh, Tae-Ho

doi:10.1111/vde.12687

Cited by 6 publications

(9 citation statements)

References 34 publications

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“…Initially, canine T lymphocytes have been stimulated shortterm via potent mitogens lectins, such as ConA (35,36) and phytohemagglutinin (PHA) (37,38) or longer-term using soluble or plate-bound anti-canine CD3 antibody alone (39)(40)(41) or in combination with CD28 antibody (6) along with IL-2 supplementation. However, naïve T lymphocytes require "two signals" of activation provided solely by APCs.…”

Section: Discussionmentioning

confidence: 99%

Effective Activation and Expansion of Canine Lymphocytes Using a Novel Nano-Sized Magnetic Beads Approach

et al. 2021

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Expansion protocols for human T lymphocytes using magnetic beads, which serve as artificial antigen presenting cells (aAPCs), is well-studied. Yet, the efficacy of magnetic beads for propagation and functionality of peripheral blood lymphocytes (PBLs) isolated from companion dogs still remains limited. Domestic dog models are important in immuno-oncology field. Thus, we built the platform for induction of canine PBLs function, proliferation and biological activity using nano-sized magnetic beads (termed as MicroBeads) coated with anti-canine CD3 and CD28 antibodies. Herein we reveal that activation of canine PBLs via MicroBeads induces a range of genes involved in immediate-early response to T cell activation in dogs. Furthermore, canine T lymphocytes are effectively activated by MicroBeads, as measured by cluster formation and induction of activation marker CD25 on canine T cells as quickly as 24 h post stimulation. Similar to human T cells, canine PBLs require lower activation signal strength for efficient proliferation and expansion, as revealed by titration studies using a range of MicroBeads in the culture. Additionally, the impact of temperature was assessed in multiple stimulation settings, showing that both 37°C and 38.5°C are optimal for the expansion of canine T cells. In contrast to stimulation using plant mitogen Concanavalin A (ConA), MicroBead-based activation did not increase activation-induced cell death. In turn, MicroBeads supported the propagation of T cells with an effector memory phenotype that secreted substantial IL-2 and IFN-γ. Thus, MicroBeads represent an accessible and affordable tool for conducting immunological studies on domestic dog models. Similarities in inducing intracellular signaling pathways further underscore the importance of this model in comparative medicine. Presented herein MicroBead-based expansion platforms for canine PBLs may benefit adoptive immunotherapy in dogs and facilitate the design of next-generation clinical trials in humans.

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Section: Discussionmentioning

confidence: 99%

Effective Activation and Expansion of Canine Lymphocytes Using a Novel Nano-Sized Magnetic Beads Approach

et al. 2021

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“…Ten atopic dogs included in the study received intravenous infusions of EBICs every two weeks for a total of six injections. This therapy was effective in reducing pruritus and objective scores of dermatitis in all dogs (Bae et al., 2018). Although the mechanism of action of EBICs was not identified, it was speculated that IFN‐γ played a role in the positive effects of EBICs.…”

Section: Ex Vivo Inflammatory Skin Disease Modelsmentioning

confidence: 99%

“…IFN‐γ‐producing cells increased significantly after ex vivo culture, although interestingly, there were no changes in IFN‐γ concentrations. The authors attributed the discrepancy to a small sample size (Bae et al., 2018). Other cytokines in AD, including IL‐4, IL‐10, and IL‐31, were not found to change in the study, and the number of T regulatory cells also did not change.…”

Section: Ex Vivo Inflammatory Skin Disease Modelsmentioning

confidence: 99%

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Canine Models of Inflammatory Skin Diseases and Their Application in Pharmacological Research

Gil,

Santoro

2023

Current Protocols

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The purpose of this article is to provide an overview of existing pharmacological models of canine dermatitis. Canine models of dermatitis have contributed significantly to our current understanding of the pathology of dermatitis and to the development of corresponding pharmacological interventions. Specifically, canine atopic dermatitis (AD) is reviewed here, as it is one of the most common inflammatory skin diseases in dogs. Canine AD also shares clinicopathological features with human AD, making the dog a natural and optimal model for human disease. Thus, pharmacological models of canine AD may be uniquely applicable to human pharmacological research. In this article, particular attention is dedicated to relevant in vivo, in vitro, and ex vivo models of canine AD, skin barrier defect models, pruritus models, and skin immunology models. Additionally, models of superficial pyoderma and food allergy are also discussed. With understanding of findings from canine models, researchers can select the most salient features for future pharmacological drug development. © 2023 Wiley Periodicals LLC.

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“…12,21,37 By contrast, four other studies on sera from client-owned dogs did not find a difference in the concentration of IL-4 between dogs with AD and healthy controls. [38][39][40][41] Since the HDMinduced experimental AD model represents the earliest stages of acute flares of AD and most client-owned dogs have more chronic lesions, it is possible that IL-4 only plays an important role during the induction or acute phase of cAD. Furthermore, it is interesting to note that the percentage of IL-4-producing T cells in dogs with AD did not change after one year of treatment with oclacitinib, despite the clinical improvement, 42 which indicates that IL-4 might be a less important inflammatory cytokine in chronic cAD.…”

Section: Interleukin-4mentioning

confidence: 99%

Update on the role of cytokines and chemokines in canine atopic dermatitis

Tamamoto-Mochizuki

Santoro

Saridomichelakis

et al. 2023

Veterinary Dermatology

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BackgroundCytokines and chemokines play central roles in the pathogenesis of canine atopic dermatitis (cAD). Numerous studies have been published and provide new insights into their roles in cAD.ObjectivesTo summarise the research updates on the role of cytokines and chemokines in the pathogenesis of cAD since the last review by the International Committee on Allergic Diseases of Animals in 2015.Material and MethodsOnline citation databases, abstracts and proceedings from international meetings on cytokines and chemokines relevant to cAD that had been published between 2015 and 2022 were reviewed.ResultsAdvances in technologies have allowed the simultaneous analysis of a broader range of cytokines and chemokines, which revealed an upregulation of a multipolar immunological axis (Th1, Th2, Th17 and Th22) in cAD. Most studies focused on specific cytokines, which were proposed as potential novel biomarkers and/or therapeutic targets for cAD, such as interleukin‐31. Most other cytokines and chemokines had inconsistent results, perhaps as a consequence of their varied involvement in the pathogenesis of different endotypes of cAD.Conclusions and Clinical RelevanceInconsistent results for many cytokines and chemokines illustrate the difficulty of studying the complex cytokine and chemokine networks in cAD, and highlight the need for more comprehensive and structured studies in the future.

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The effect of an ex vivo boosted immune cell therapy on canine atopic dermatitis: an open, uncontrolled pilot study

Abstract: EBIC therapy is a safe and efficient treatment for cAD. This therapy could correct the immunological imbalance in dogs with AD by infusing activated T lymphocytes.

Cited by 6 publications

References 34 publications

Effective Activation and Expansion of Canine Lymphocytes Using a Novel Nano-Sized Magnetic Beads Approach

Effective Activation and Expansion of Canine Lymphocytes Using a Novel Nano-Sized Magnetic Beads Approach

Canine Models of Inflammatory Skin Diseases and Their Application in Pharmacological Research

Update on the role of cytokines and chemokines in canine atopic dermatitis

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