Atializumab, a humanized anti-aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) antibody significantly improves nephritis in (NZB/NZW) F1 mice

Mun, Chin Hee; Kim, Jin Ock; Ahn, Sung Soo; Yoon, Taejun; Kim, Su Jeong; Ko, Eunkyung; Noh, Hee Dong; Park, Yong Bum; Jung, Hak Jun; Kim, Tae Sung; Lee, Sang Won; Park, Sang Gyu

doi:10.1016/j.biomaterials.2019.119408

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…NN2101, a fully human monoclonal IgG1, was prepared as described previously [ 43 ]. Briefly, DNA sequences encoding the light and heavy chains were subcloned into the pCHO 1.0 vector (Thermo Fisher Scientific, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

A novel anti‐c‐Kit antibody–drug conjugate to treat wild‐type and activating‐mutant c‐Kit‐positive tumors

Kim

Baek

et al. 2021

Molecular Oncology

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c-Kit overexpression and activating mutations, which are reported in various cancers, including gastrointestinal stromal tumor (GIST), small-cell lung cancer (SCLC), acute myeloid leukemia, acral melanoma, and systemic mastocytosis (SM), confer resistance to tyrosine kinase inhibitors (TKIs). To overcome TKI resistance, an anti-c-Kit antibody-drug conjugate was developed in this study to treat wild-type and mutant c-Kitpositive cancers. NN2101, a fully human IgG1, was conjugated to DM1, a microtubule inhibitor, through N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) (to give NN2101-DM1). The antitumor activity of NN2101-DM1 was evaluated in vitro and in vivo using various cancer cell lines. NN2101-DM1 exhibited potent growth-inhibitory activities against c-Kit-positive cancer cell lines. In a mouse xenograft model, NN2101-DM1 exhibited potent growth-inhibitory activities against imatinib-resistant GIST and SM cells. In addition, NN2101-DM1 exhibited a significantly higher anti-cancer effect than carboplatin/etoposide against SCLC cells where c-Kit does not mediate cancer pathogenesis. Furthermore, the combination of NN2101-DM1 with imatinib in imatinib-sensitive GIST cells induced complete remission compared with treatment with NN2101-DM1 or imatinib alone in mouse xenograft models. These results suggest that NN2101-DM1 is a potential therapeutic agent for wild-type and mutant c-Kit-positive cancers.

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Section: Methodsmentioning

confidence: 99%

A novel anti‐c‐Kit antibody–drug conjugate to treat wild‐type and activating‐mutant c‐Kit‐positive tumors

Kim

Baek

et al. 2021

Molecular Oncology

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“…Elevated serum levels of AIMp1 have been reported in SLE patients and are predictive of active disease (117). Treatment with AIMp1 targeting antibody atializumab significantly reduced the severity of nephritis symptoms including proteinuria, glomerular damage, and renal deposition of immune complex in lupus-prone mice (NZB/NZW) (118). Atializumab also reduced proinflammatory cytokines including IFN-g, IL-17A, and IL-6.…”

Section: The Mars Complex and Immune Diseasementioning

confidence: 96%

“…In contrast, anti-inflammatory responses that included upregulation of IL-10 secreting Tregs were significantly increased by atializumab treatment. As AIMp1 is reported to mediate proinflammatory responses via NFkB, its inhibition by atializumab predictably suppressed NFkB activation by inhibiting Ikba degradation (118).…”

Section: The Mars Complex and Immune Diseasementioning

confidence: 98%

The mARS complex: a critical mediator of immune regulation and homeostasis

Amanya,

Oyewole-Said,

Ernste

et al. 2024

Front. Immunol.

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Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular organisms is hypothesized. While mARS complexes in lower eukaryotes may enhance efficiency of aminoacylation, little evidence exists to support a similar role in chordates or other higher eukaryotes. Rather, mARS complexes are reported to regulate multiple and variegated cellular processes that include angiogenesis, apoptosis, inflammation, anaphylaxis, and metabolism. Because all such processes are critical components of immune homeostasis, it is important to understand the role of mARS complexes in immune regulation. Here we provide a conceptual analysis of the current understanding of mARS complex dynamics and emerging mARS complex roles in immune regulation, the increased understanding of which should reveal therapeutic targets in immunity and immune-mediated disease.

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“…Immune abnormalities interact with various other factors, leading to a decrease in T lymphocytes and a decline in Treg cell function in SLE ( 310 ). LN is an autoimmune disease secondary to SLE, characterized by cell proliferation and immune complex deposition, accompanied by significant clinical manifestations of renal damage ( 311 ). Studies have demonstrated that the metabolic patterns of Th17 cells and Treg cells affect the balance of both cell types ( 312 ) ( Figure 5 ).…”

Section: Renal Microenvironmentmentioning

confidence: 99%

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

Han

Tao

et al. 2022

Front. Immunol.

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Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

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Atializumab, a humanized anti-aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) antibody significantly improves nephritis in (NZB/NZW) F1 mice

Cited by 10 publications

References 40 publications

A novel anti‐c‐Kit antibody–drug conjugate to treat wild‐type and activating‐mutant c‐Kit‐positive tumors

A novel anti‐c‐Kit antibody–drug conjugate to treat wild‐type and activating‐mutant c‐Kit‐positive tumors

The mARS complex: a critical mediator of immune regulation and homeostasis

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

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