AS2762900-00, a potent anti-human IL-23 receptor monoclonal antibody, prevents epidermal hyperplasia in a psoriatic human skin xenograft model

Sasaki-Iwaoka, Haruna; Taguchi, K; Okada, Yohei; Imamura, Emiko; Kubo, Satoshi; Furukawa, Shigetada; Morokata, Tatsuaki

doi:10.1016/j.ejphar.2018.11.030

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…One possible explanation for these unexpected results is the use of tissue samples of inappropriate time points. We note in this regard that Sasaki‐Iwaoka et al (2019) were also unable to observe down‐regulation of Il17a by an IL‐23 receptor antibody in the same psoriasis model.…”

Section: Discussionmentioning

confidence: 63%

Repurposing the anthelmintic praziquantel to treat psoriasis

Hao

Mao

Park

et al. 2021

British J Pharmacology

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Background and Purpose The anthelmintic drug praziquantel has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose praziquantel to treat psoriasis. Experimental Approach Psoriasis‐like skin inflammation was induced in mice (C57 and Balb/C) by topical application of imiquimod or intradermal injection of recombinant IL‐23. Praziquantel was either orally or topically administered during the psoriasis induction period. Key Results Mice treated with either oral or topical praziquantel exhibited markedly improved psoriasiform skin symptoms when compared with control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that praziquantel inhibited STAT3 phosphorylation and RORγt expression in splenic CD4+ T‐cells. Praziquantel also decreased STAT3 phosphorylation in HEK‐A/F cells. Down‐regulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes. Conclusion and Implications These results provide the first preclinical evidence that praziquantel may effectively treat psoriasis, and suggest that praziquantel alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.

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Section: Discussionmentioning

confidence: 63%

Repurposing the anthelmintic praziquantel to treat psoriasis

Hao

Mao

Park

et al. 2021

British J Pharmacology

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“… 31 , 32 , 33 abEC1.1 and other mAbs are promising drug candidates for the treatment of genodermatoses. 34 , 35 , 36 , 37 Seminal work in mice treated with a recombinant mAb-encoding adeno-associated virus (AAV) vector showed sustained mAb levels in the circulation, using the AAV8 serotype that efficiently transduces the liver. 38 This procedure, known as antibody gene transfer, allows direct antibody production and secretion within the body that necessitates treatment.…”

Section: Introductionmentioning

confidence: 99%

Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice

et al. 2023

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“…In one study, T-cells were identified and IL-1β and IFN-γ were expressed in the grafts after repeated co-injections of PBMCs beneath the grafts [ 7 ]. In other studies, intradermal injections of PBMCs in symptomless skin from psoriasis patients induced a psoriatic phenotype in the grafts [ 2 , 12 , 13 ]. Of these, only one study investigated the T-cell activity in the grafts [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In other studies, intradermal injections of PBMCs in symptomless skin from psoriasis patients induced a psoriatic phenotype in the grafts [ 2 , 12 , 13 ]. Of these, only one study investigated the T-cell activity in the grafts [ 13 ]. In this study IL-17A and IL-17F were expressed and treatment with an anti-human IL-23 receptor mAb reduced the epidermal thickness, inflammatory cell infiltration and CK16 expression score.…”

Section: Introductionmentioning

confidence: 99%

Sustaining the T-cell activity in xenografted psoriasis skin

et al. 2023

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Xenografting of psoriasis skin onto immune deficient mice has been widely used to obtain proof-of-principle of new drug candidates. However, the lack of human T-cell activity in the grafts limits the use of the model. Here, we show that xenografting of lesional skin from psoriasis patients onto human IL-2 NOG mice results in increased numbers of human CD3+ cells in the grafts, axillary lymph nodes and blood from human IL-2 NOG mice compared to C.B-17 scid and NOG mice. In addition, disease relevant human cytokine levels were higher in graft lysates and serum from human IL-2 NOG mice. However, the epidermis was lacking and no efficacy of ustekinumab, a human anti-P40 antibody targeting both IL-12 and IL-23, was shown. Thus, despite the sustained T-cell activity, the model needs further investigations and validation to capture more aspects of psoriasis.

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AS2762900-00, a potent anti-human IL-23 receptor monoclonal antibody, prevents epidermal hyperplasia in a psoriatic human skin xenograft model

Cited by 4 publications

References 31 publications

Repurposing the anthelmintic praziquantel to treat psoriasis

Repurposing the anthelmintic praziquantel to treat psoriasis

Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice

Sustaining the T-cell activity in xenografted psoriasis skin

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