Sustained secretion of anti‐tumor necrosis factor α monoclonal antibody from <i>ex vivo</i> genetically engineered dermal tissue demonstrates therapeutic activity in mouse model of rheumatoid arthritis

Zafir-Lavie, Inbal; Miari, Reem; Sherbo, Shay; Krispel, Simi; Tal, Osnat; Liran, Atar; Shatil, Tamar; Badinter, Felix; Goltsman, Haim; Shapir, Nir; Benhar, Itai; Neil, Garry A.; Panet, Amos

doi:10.1002/jgm.2965

Cited by 4 publications

(1 citation statement)

References 51 publications

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“…By referring to the results of these pharmacokinetic studies and previous in vivo studies using murine arthritis models, an equivalent dose for mouse administration based on body surface area was calculated, and an effective dosage range to suppress the systemic inflammatory status with minimum side effects was chosen for each antirheumatic regent ( Nair and Jacob, 2016 ). The doses were 0.25 or 0.5 mg/kg for methotrexate ( Singh et al., 2019 ), 0.1 or 0.2 mg/kg for prednisolone ( Hofkens et al., 2011 ), 0.75 or 1.5 mg/kg for adalimumab ( Zafir-Lavie et al., 2017 ), and 4 or 8 mg/kg for tocilizumab ( Thiolat et al., 2014 ). Mice implanted with saline-filled pumps were used as controls.…”

Section: Methodsmentioning

confidence: 99%

Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells

et al. 2020

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Mesenchymal stem cell (MSC)-based articular regeneration might be beneficial for both protecting and rebuilding cartilaginous tissues in the management of rheumatoid arthritis. However, it is unclear how current immunosuppressive strategies influence the multipotency of MSCs. The present study was undertaken to profile the direct effectiveness of major antirheumatic drugs including methotrexate, prednisolone, adalimumab, and tocilizumab on the multipotency of MSCs, with a special focus on chondrogenesis. The inhibitory effects of methotrexate on adipogenesis, osteogenesis, and chondrogenesis were observed to occur in a dose-dependent manner in an in vitro differentiation system. Prednisolone enhanced adipogenesis, but reduced alkaline phosphatase activity in osteoprogenitors and suppressed the formation of chondrospheroids. Adalimumab suppressed alkaline phosphatase activity, while tocilizumab diminished osteogenesis and chondrogenesis of MSCs in vitro. Chondrogenesis of antirheumatic drug-treated MSCs was also evaluated in vivo using a scaffolded spheroid-engrafted murine model. The biologics examined appeared to be relatively safe for cartilaginous formation, but methotrexate and prednisolone exhibited opposing influences on chondrogenesis. Taken together, these results reveal the direct efficacy of major antirheumatic agents on the multipotency of MSCs. Therefore, our findings suggest that optimization of medication protocols is further required for therapeutic approaches involving cartilaginous tissue engineering.

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Section: Methodsmentioning

confidence: 99%

Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells

et al. 2020

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Successful intracranial delivery of trastuzumab by gene-therapy for treatment of HER2-positive breast cancer brain metastases

Zafir-Lavie

Sherbo

Goltsman

et al. 2018

Journal of Controlled Release

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Monoclonal Antibodies: A Prospective and Retrospective View

Sivaccumar

Sandomenico

Vitagliano

et al. 2021

CMC

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Background: Monoclonal antibodies (mAbs) represent one of the most important classes of biotherapeutic agents. They are used to cure many diseases, including cancer, autoimmune diseases, cardiovascular diseases, angiogenesis-related diseases and more recently also haemophilia. They can be highly varied in terms of format, source, and specificity to improve efficacy and to obtain more targeted applications. This can be achieved by leaving substantially unchanged the basic structural components for paratope clustering. Objectives: The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends. Results: We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables. Conclusions: The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.

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Sustained secretion of anti‐tumor necrosis factor α monoclonal antibody from ex vivo genetically engineered dermal tissue demonstrates therapeutic activity in mouse model of rheumatoid arthritis

Cited by 4 publications

References 51 publications

Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells

Assessment and Comparison of the Efficacy of Methotrexate, Prednisolone, Adalimumab, and Tocilizumab on Multipotency of Mesenchymal Stem Cells

Successful intracranial delivery of trastuzumab by gene-therapy for treatment of HER2-positive breast cancer brain metastases

Monoclonal Antibodies: A Prospective and Retrospective View

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